Genome-wide association studies identify 137 genetic loci for DNA methylation biomarkers of aging

Abstract Background Biological aging estimators derived from DNA methylation data are heritable and correlate with morbidity and mortality. Consequently, identification of genetic and environmental contributors to the variation in these measures in populations has become a major goal in the field. Results Leveraging DNA methylation and SNP data from more than 40,000 individuals, we identify 137 genome-wide significant loci, of which 113 are novel, from genome-wide association study (GWAS) meta-analyses of four epigenetic clocks and epigenetic surrogate markers for granulocyte proportions and plasminogen activator inhibitor 1 levels, respectively. We find evidence for shared genetic loci ass…

Does higher education protect against obesity? Evidence using Mendelian randomization

Objectives. The aim of this explorative study was to examine the effect of education on obesity using Mendelian randomization. Methods. Participants (N = 2011) were from the on- going nationally representative Young Finns Study (YFS) that began in 1980 when six cohorts (aged 30, 33, 36, 39, 42 and 45 in 2007) were recruited. The average value of BMI (kg/m(2)) measurements in 2007 and 2011 and genetic information were linked to comprehensive register based information on the years of education in 2007. We first used a linear regression (Ordinary Least Squares, OLS) to estimate the relationship between education and BMI. To identify a causal relationship, we exploited Mendelian randomization …

Stature and long-term labor market outcomes: Evidence using Mendelian randomization.

We use the Young Finns Study (N = ∼2000) on the measured height linked to register-based long-term labor market outcomes. The data contain six age cohorts (ages 3, 6, 9, 12, 15 and 18, in 1980) with the average age of 31.7, in 2001, and with the female share of 54.7. We find that taller people earn higher earnings according to the ordinary least squares (OLS) estimation. The OLS models show that 10 cm of extra height is associated with 13% higher earnings. We use Mendelian randomization, with the genetic score as an instrumental variable (IV) for height to account for potential confounders that are related to socioeconomic background, early life conditions and parental investments, which ar…

Genetic association study of childhood aggression across raters, instruments, and age

AbstractChildhood aggressive behavior (AGG) has a substantial heritability of around 50%. Here we present a genome-wide association meta-analysis (GWAMA) of childhood AGG, in which all phenotype measures across childhood ages from multiple assessors were included. We analyzed phenotype assessments for a total of 328 935 observations from 87 485 children aged between 1.5 and 18 years, while accounting for sample overlap. We also meta-analyzed within subsets of the data, i.e., within rater, instrument and age. SNP-heritability for the overall meta-analysis (AGGoverall) was 3.31% (SE = 0.0038). We found no genome-wide significant SNPs for AGGoverall. The gene-based analysis returned three sign…

Long-term determinants of changes in television viewing time in adults: Prospective analyses from the Young Finns Study

Purpose The long-term effects of sociodemographic and health characteristics on television viewing (TV) time changes have not been identified in adulthood. We aimed to examine the modifiable and non-modifiable determinants of changes in TV-time in young adults over 10 years. Methods Participants (N = 2929) aged 24-39 years were recruited between 2001 and 2011 from the Cardiovascular Risk in Young Finns Study. Data were collected using questionnaires and a medical examination. The determinants of changes in TV-time were estimated using latent growth modeling for men and women separately. Results For men, inverse associations with initial levels of TV-time were observed for students becoming …

Associations of Leisure-Time Physical Activity Trajectories with Fruit and Vegetable Consumption from Childhood to Adulthood: The Cardiovascular Risk in Young Finns Study.

A physically active lifestyle and a diet rich in vegetables and fruits have a central role in promoting health. This study examined the associations between leisure-time physical activity (LTPA) trajectories and fruit and vegetable consumption (FVC) from childhood to middle age. The data were drawn from the Cardiovascular Risk in Young Finns Study with six age cohorts. Participants were 9 to 18 years (n = 3536

Factors associated with six-year weight change in young and middle-aged adults in the Young Finns Study

Objective. To examine factors associated with weight change and obesity risk in young and middle-aged adults. Subjects/methods. The Young Finns Study with its 923 women and 792 men aged 24–39 years at baseline were followed for six years. Variables associated with the weight change were investigated with regression models. Results. The average weight change was 0.45 kg/year in women and 0.58 kg/year in men. In women, weight change was steady across all ages. In men, weight changes were more pronounced in younger age groups. In women (weight gain > 2 kg, n = 490), medication for anxiety, low occupational status, high baseline BMI (body mass index), high intake of sweet beverages, high chi…

Physical inactivity from youth to adulthood and adult cardiometabolic risk profile

Adults with a low physical activity (PA) level are at increased risk for cardiometabolic diseases, but little is known on the association between physical inactivity since youth and cardiometabolic health in adulthood. We investigated the association of persistent physical inactivity from youth to adulthood with adult cardiometabolic risk factors. Data were drawn from the ongoing Cardiovascular Risk in Young Finns Study with seven follow-ups between 1980 and 2011 (baseline age 3–18 years, n = 1961). Physical activity data from a standardized questionnaire was expressed as a PA-index. Using the PA-index, four groups were formed: 1)persistently physically inactive (n = 246), 2)decreasingly ac…

Heterogeneous contributions of change in population distribution of body mass index to change in obesity and underweight

From 1985 to 2016, the prevalence of underweight decreased, and that of obesity and severe obesity increased, in most regions, with significant variation in the magnitude of these changes across regions. We investigated how much change in mean body mass index (BMI) explains changes in the prevalence of underweight, obesity, and severe obesity in different regions using data from 2896 population-based studies with 187 million participants. Changes in the prevalence of underweight and total obesity, and to a lesser extent severe obesity, are largely driven by shifts in the distribution of BMI, with smaller contributions from changes in the shape of the distribution. In East and Southeast Asia…

Sustained participation in youth sport decreases metabolic syndrome in adulthood.

to explore the effect of organized youth sport on metabolic syndrome (MetS) in adulthood. Longitudinal study data from the cardiovascular risk in young Finns study. A total of 1493 males (n=704) and females (n=789) aged 3, 6, 9, 12, 15 and 18 years were randomly selected from five university towns and their rural surroundings in 1980. They were followed up for 21 years. In 2001 they were 24, 27, 30, 33, 36 and 39 years old. Youth sports participation data (participation in sport-club training and competitions) were assessed in 1980 and 1983 using a self-report questionnaire completed in connection with a medical examination. Participants were divided into athletes and non-athletes at each m…

Genome-wide meta-analyses of multiancestry cohorts identify multiple new susceptibility loci for refractive error and myopia

Author version made available in accordance with the publisher's policy.

Author response: Heterogeneous contributions of change in population distribution of body mass index to change in obesity and underweight

Cohort profile: the cardiovascular risk in Young Finns Study.

In Finland, coronary heart disease (CHD) incidence was very high in the 1960s and 1970s. In line with this high incidence, the Seven Countries Study showed that the level of serum cholesterol in Finns was also the highest among the investigated countries in the 1960s. Because several studies indicated that the atherosclerotic process starts early in life, and in accord with the World Health Organization Recommendation of 1978 which stated that studies assessing atherosclerosis precursors in children should be initiated, a program was launched in Finland in the late 1970s to study cardiovascular risk in the youth. The Cardiovascular Risk in Young Finns Study was designed as a collaborative e…

Born entrepreneurs? : Adolescents’ personality characteristics and entrepreneurship in adulthood

Is there an entrepreneurial personality, and does it appear early in life? We provide a new answer to this important question by examining traits related to Type A behavior (Aggression, Leadership, Responsibility, and Eagerness-Energy) measured during adolescence and their relationship to entrepreneurship propensity in adulthood. The results indicate that the early-life Leadership dimension is significantly associated with a higher likelihood of 1) becoming an entrepreneur and 2) being more successful as an entrepreneur, as approximated by sales. peerReviewed

Association of Birth Weight With Type 2 Diabetes and Glycemic Traits: A Mendelian Randomization Study.

Key Points Question Is birth weight associated with type 2 diabetes and glycemic traits? Findings This mendelian randomization study found that a 1-SD decrease in birth weight due to the genetic risk score was associated with a higher risk of type 2 diabetes among European and East Asian populations. In addition, a 1-SD decrease in birth weight was associated with a 0.189-SD increase in fasting glucose concentration, but not with fasting insulin, 2-hour glucose, or hemoglobin A1c level. Meaning A genetic predisposition to lower birth weight was associated with an increased risk of type 2 diabetes and increased fasting glucose, suggesting potential mechanisms through which perturbation of th…

Daily steps among Finnish adults: Variation by age, sex, and socioeconomic position

Aims: The aim of this study was to provide descriptive population-based pedometer data from adults aged 30-45 years in Finland, and to compare daily step counts with evidence-based indices. Methods: The data was collected from 1853 participants in 7 consecutive days in winter 2007—08 in part of 27-year follow up of the Cardiovascular Risk in Young Finns study. Results: The participants took (mean±standard deviation) 7499 ± 2908 steps/day. Step counts included 1925 ± 2052 aerobic steps/day gathered in bouts of at least 10 min continuous ambulatory activity. Women had more total steps than men ((7824 ± 2925 vs. 7089 ± 2774; p < 0.001). Although participants had higher mean total steps on …

Education Leads to a More Physically Active Lifestyle : Evidence Based on Mendelian Randomization

Physical inactivity is a major health risk worldwide. Observational studies suggest that higher education is positively related to physical activity, but it is not clear whether this relationship constitutes a causal effect. Using participants (N = 1651) drawn from the Cardiovascular Risk in Young Finns Study linked to nationwide administrative data from Statistics Finland, this study examined whether educational attainment, measured by years of education, is related to adulthood physical activity in terms of overall physical activity, weekly hours of intensive activity, total steps per day, and aerobic steps per day. We employed ordinary least squares (OLS) models and extended the analysis…

Tracking of Television Viewing Time during Adulthood: The Young Finns Study.

Purpose: The aim of this study was to investigate the tracking of television viewing (TV) time as an indicator of sedentary behavior among adults for a period of 25 yr. Methods: A random sample of 1601 subjects (740 men) age 18, 21, and 24 yr participated in the Cardiovascular Risk in Young Finns Study in 1986. TV time during leisure time was measured with a single self-report question at baseline and in 2001, 2007, and 2011. Tracking of TV time was analyzed using Spearman rank correlations and simplex models. Level and change of TV time were examined using linear growth modeling. Results: The 4- and 6-yr integrated TV time stability coefficients, adjusted for measurement errors, were Q0.60…

Meta-analysis of genome-wide association studies from the CHARGE consortium identifies common variants associated with carotid intima media thickness and plaque

Carotid intima media thickness (cIMT) and plaque determined by ultrasonography are established measures of subclinical atherosclerosis that each predicts future cardiovascular disease events. We conducted a meta-analysis of genome-wide association data in 31,211 participants of European ancestry from nine large studies in the setting of the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Consortium. We then sought additional evidence to support our findings among 11,273 individuals using data from seven additional studies. In the combined meta-analysis, we identified three genomic regions associated with common carotid intima media thickness and two different regions a…

A Genome-Wide Screen for Interactions Reveals a New Locus on 4p15 Modifying the Effect of Waist-to-Hip Ratio on Total Cholesterol

Recent genome-wide association (GWA) studies described 95 loci controlling serum lipid levels. These common variants explain ∼25% of the heritability of the phenotypes. To date, no unbiased screen for gene–environment interactions for circulating lipids has been reported. We screened for variants that modify the relationship between known epidemiological risk factors and circulating lipid levels in a meta-analysis of genome-wide association (GWA) data from 18 population-based cohorts with European ancestry (maximum N = 32,225). We collected 8 further cohorts (N = 17,102) for replication, and rs6448771 on 4p15 demonstrated genome-wide significant interaction with waist-to-hip-ratio (WHR) on …

Genetic analyses of the QT interval and its components in over 250K individuals identifies new loci and pathways affecting ventricular depolarization and repolarization

AbstractThe QT interval is an electrocardiographic measure representing the sum of ventricular depolarization (QRS duration) and repolarization (JT interval). Abnormalities of the QT interval are associated with potentially fatal ventricular arrhythmia. We conducted genome-wide multi-ancestry analyses in >250,000 individuals and identified 177, 156 and 121 independent loci for QT, JT and QRS, respectively, including a male-specific X-chromosome locus. Using gene-based rare-variant methods, we identified associations with Mendelian disease genes. Enrichments were observed in established pathways for QT and JT, with new genes indicated in insulin-receptor signalling and cardiac energy meta…

Systemic vascular resistance predicts the development of hypertension : the cardiovascular risk in young Finns study

To study whether systemic hemodynamics, especially systemic vascular resistance, predicts the development of hypertension and improves the risk prediction of incident hypertension beyond common risk factors in the risk models in young adults. Typical risk factors for hypertension in the risk prediction models (systolic and diastolic blood pressure, parental history of hypertension, age, sex, body-mass index, smoking), laboratory values (high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, triglycerides, glucose, insulin, C-reactive protein), heart rate (HR), stroke index (SI), and systemic vascular resistance index (SVRI) calculated by whole-body impedance cardiography…

Schizophrenia polygenic risk score and long-term success in the labour market: A cohort study

Publisher Copyright: © 2022 The Authors Employment is rare among people with a schizophrenia diagnosis. Meanwhile, a genetic liability for schizophrenia may hinder labour market performance. We studied how the polygenic risk score (PGS) for schizophrenia related to education and labour market outcomes. We found that a higher PGS was linked to lower educational levels and weaker labour market outcomes as well as a higher likelihood of receiving social income transfers, particularly among men. Assuming that the link is causal, our results indicate that individuals with schizophrenia or schizophrenia-related traits have a weakened ability to fully participate in the labour market, potentially …

Childhood Nutrition in Predicting Metabolic Syndrome in Adults

OBJECTIVE Our aim was to study the associations of childhood lifestyle factors (the frequency of consumption of vegetables, fruit, fish, and meat, butter use on bread, and physical activity) with the metabolic syndrome (MetS) in adulthood. RESEARCH DESIGN AND METHODS The study cohort consisted of 2,128 individuals, 3–18 years of age at the baseline, with a follow-up time of 27 years. We used the average of lifestyle factor measurements taken in 1980, 1983, and 1986 in the analyses. Childhood dietary factors and physical activity were assessed by self-reported questionnaires, and a harmonized definition of MetS was used as the adult outcome. RESULTS Childhood vegetable consumption frequency…

Meta-analysis of gene-environment-wide association scans accounting for education level identifies additional loci for refractive error

Myopia is the most common human eye disorder and it results from complex genetic and environmental causes. The rapidly increasing prevalence of myopia poses a major public health challenge. Here, the CREAM consortium performs a joint meta-analysis to test single-nucleotide polymorphism (SNP) main effects and SNP × education interaction effects on refractive error in 40,036 adults from 25 studies of European ancestry and 10,315 adults from 9 studies of Asian ancestry. In European ancestry individuals, we identify six novel loci (FAM150B-ACP1, LINC00340, FBN1, DIS3L-MAP2K1, ARID2-SNAT1 and SLC14A2) associated with refractive error. In Asian populations, three genome-wide significant loci AREG…

Novel loci for childhood body mass index and shared heritability with adult cardiometabolic traits

The genetic background of childhood body mass index (BMI), and the extent to which the well-known associations of childhood BMI with adult diseases are explained by shared genetic factors, are largely unknown. We performed a genome-wide association study meta-analysis of BMI in 61,111 children aged between 2 and 10 years. Twenty-five independent loci reached genome-wide significance in the combined discovery and replication analyses. Two of these, located nearNEDD4LandSLC45A3, have not previously been reported in relation to either childhood or adult BMI. Positive genetic correlations of childhood BMI with birth weight and adult BMI, waist-to-hip ratio, diastolic blood pressure and type 2 d…

Does organized sport participation during youth predict healthy habits in adulthood? A 28-year longitudinal study

Health behaviors in youth can predict the same behaviors later in life, but the role of sport participation in predicting healthy lifestyle habits is unclear. This study aimed to investigate the association between participation in organized youth sport and adult healthy lifestyle habits. Data from the longitudinal Cardiovascular Risk in Young Finns Study (YFS) with a 28-year follow-up were used. The participation in sport-club training sessions was self-reported by 9-18-year-olds in 1983 and 1986 (n = 1285). During 2011, participants (aged 37-43-year old) reported their smoking status, alcohol consumption, fruit and vegetable consumption, and physical activity. Odd ratios (OR) were calcula…

Childhood Physical Activity and Adulthood Earnings

Purpose: This study examined the associations between childhood physical activity level and adulthood earnings. Methods: The data were drawn from the ongoing longitudinal Young Finns Study, which was combined with register-based Finnish Longitudinal Employer–Employee Data and registerbased parents_ background information from the Longitudinal Population Census of Statistics Finland. The study consisted of children who were 9 yr (n = 1257, 52% boys), 12 yr (n = 1662, 51% boys), and 15 yr (n = 1969, 49% boys) of age at the time when physical activity was measured. The children were followed until 2010, when they were between 33 and 45 yr old. Leisure-time physical activity in childhood was se…

Harmonization of Neuroticism and Extraversion phenotypes across inventories and cohorts in the Genetics of Personality Consortium:an application of Item Response Theory

Mega- or meta-analytic studies (e.g. genome-wide association studies) are increasingly used in behavior genetics. An issue in such studies is that phenotypes are often measured by different instruments across study cohorts, requiring harmonization of measures so that more powerful fixed effect meta-analyses can be employed. Within the Genetics of Personality Consortium, we demonstrate for two clinically relevant personality traits, Neuroticism and Extraversion, how Item-Response Theory (IRT) can be applied to map item data from different inventories to the same underlying constructs. Personality item data were analyzed in >160,000 individuals from 23 cohorts across Europe, USA and Australia…

Prospective relationship of change in ideal cardiovascular health status and arterial stiffness: the Cardiovascular Risk in Young Finns Study.

Background In 2010, the American Heart Association defined ideal cardiovascular health as the simultaneous presence of 4 favorable health behaviors (nonsmoking, ideal body mass index, physical activity at goal, and dietary pattern that promotes cardiovascular health) and 3 favorable health factors (ideal levels of total cholesterol, blood pressure, and fasting glucose). The association between a change in ideal cardiovascular health status and pulse wave velocity, a surrogate marker of cardiovascular disease, has not been reported. Methods and Results The study cohort consisted of 1143 white adults from the Cardiovascular Risk in Young Finns Study who were followed for 21 years since basel…

Childhood physical activity as a labor market investment

This study examined the role of physical activity and changes in physical activity levels during childhood in long-term labor market outcomes. To address this important but under-researched theme, the study utilized data drawn from longitudinal research, the Cardiovascular Risk in Young Finns Study (YFS), and from registries compiled by Statistics Finland. The study consisted of children aged 9 (n = 1565) and 15 (n = 2445) at the time their physical activity was measured. Labor market outcomes, including employment status, average employment months, and average unemployment months, were calculated from 1997 to 2010, when the participants were aged 20 to 48 years. Regression models were used…

Genome-wide association analyses identify 18 new loci associated with serum urate concentrations

Elevated serum urate concentrations can cause gout, a prevalent and painful inflammatory arthritis. By combining data from >140,000 individuals of European ancestry within the Global Urate Genetics Consortium (GUGC), we identified and replicated 28 genome-wide significant loci in association with serum urate concentrations (18 new regions in or near TRIM46, INHBB, SFMBT1, TMEM171, VEGFA, BAZ1B, PRKAG2, STC1, HNF4G, A1CF, ATXN2, UBE2Q2, IGF1R, NFAT5, MAF, HLF, ACVR1B-ACVRL1 and B3GNT4). Associations for many of the loci were of similar magnitude in individuals of non-European ancestry. We further characterized these loci for associations with gout, transcript expression and the fractional…

Maternal and fetal genetic effects on birth weight and their relevance to cardio-metabolic risk factors

AbstractBirth weight (BW) variation is influenced by fetal and maternal genetic and non-genetic factors, and has been reproducibly associated with future cardio-metabolic health outcomes. These associations have been proposed to reflect the lifelong consequences of an adverse intrauterine environment. In earlier work, we demonstrated that much of the negative correlation between BW and adult cardio-metabolic traits could instead be attributable to shared genetic effects. However, that work and other previous studies did not systematically distinguish the direct effects of an individual’s own genotype on BW and subsequent disease risk from indirect effects of their mother’s correlated genoty…

Associations of parental physical activity trajectories with offspring's physical activity patterns from childhood to middle adulthood : The Young Finns Study

We investigated the association of parental physical activity (PA) trajectories with offspring's youth and adult PA. Self-reported PA data were extracted from the Young Finns Study with three follow-ups for parents between 1980 and 1986 and nine follow-ups for their offspring in youth between 1980 and 2011 (aged 9-39 years, n = 2402) and in adulthood in 2018. Accelerometer-derived PA was quantified in 2018-2020 (aged 43-58 years, n = 1134). Data were analyzed using mixture models and conducted in 2022. We identified three trajectories for fathers and mothers (high-stable activity, 20.2%/16.6%; moderate-stable activity, 50.5%/49.6%; and low-stable activity, 29.4%/33.7%) and four for youth ma…

The biometric antecedents to happiness

It has been suggested that biological markers are associated with human happiness. We contribute to the empirical literature by examining the independent association between various aspects of biometric wellbeing measured in childhood and happiness in adulthood. Using Young Finns Study data (n = 1905) and nationally representative linked data we examine whether eight biomarkers measured in childhood (1980) are associated with happiness in adulthood (2001). Using linked data we account for a very rich set of confounders including age, sex, body size, family background, nutritional intake, physical activity, income, education and labour market experiences. We find that there is a negative rel…

Influential Periods in Longitudinal Clinical Cardiovascular Health Scores

Abstract The prevalence of ideal cardiovascular health (CVH) among adults in the United States is low and decreases with age. Our objective was to identify specific age windows when the loss of CVH accelerates, to ascertain preventive opportunities for intervention. Data were pooled from 5 longitudinal cohorts (Project Heartbeat!, Cardiovascular Risk in Young Finns Study, The Bogalusa Heart Study, Coronary Artery Risk Development in Young Adults, Special Turku Coronary Risk Factor Intervention Project) from the United States and Finland from 1973 to 2012. Individuals with clinical CVH factors (i.e., body mass index, blood pressure, cholesterol, blood glucose) measured from ages 8 to 55 year…

Prolonged sleep restriction induces changes in pathways involved in cholesterol metabolism and inflammatory responses

Article

Genetic endowments, parental resources and adult health: Evidence from the Young Finns Study

This paper uses longitudinal survey data linked to administrative registers to examine socioeconomic gradients in health, particularly whether the effects of genetic endowments interact with the socioeconomic resources of the parental household. We find that genetic risk scores contribute to adult health measured by biomarkers. This result is consistent with the findings from genome-wide association studies. Socioeconomic gradients in health differ based on biomarker and resource measures. Family education is negatively related to obesity and the waist-hip ratio, and family income is negatively related to low-density lipoprotein cholesterol and triglyceride levels. Parental resources do not…

Influence of early life risk factors and lifestyle on systemic vascular resistance in later adulthood : the cardiovascular risk in young Finns study

Purpose: There are limited data available concerning the effects of lifetime risk factors and lifestyle on systemic hemodynamics, especially on systemic vascular resistance. The purpose of the study was to evaluate how lifetime cardiovascular risk factors (body mass index (BMI), high-density lipoprotein, low-density lipoprotein, triglycerides, systolic blood pressure, blood glucose) and lifestyle factors (vegetable consumption, fruit consumption, smoking and physical activity) predict systemic vascular resistance index (SVRI) and cardiac index (CI) assessed in adulthood. Materials and Methods: Our study cohort comprised 1635 subjects of the Cardiovascular Risk in Young Finns Study followed …

Long-term determinants of changes in television viewing time in adults : Prospective analyses from the Young Finns Study

Purpose: The long‐term effects of sociodemographic and health characteristics on television viewing (TV) time changes have not been identified in adulthood. We aimed to examine the modifiable and non‐modifiable determinants of changes in TV‐time in young adults over 10 years.Methods: Participants (N = 2929) aged 24‐39 years were recruited between 2001 and 2011 from the Cardiovascular Risk in Young Finns Study. Data were collected using questionnaires and a medical examination. The determinants of changes in TV‐time were estimated using latent growth modeling for men and women separately.Results: For men, inverse associations with initial levels of TV‐time were observed for students becoming…

Childhood Environmental and Genetic Predictors of Adulthood Obesity: The Cardiovascular Risk in Young Finns Study

Obesity from childhood to adulthood is associated with adverse health later in life. Increased youth BMI is a risk factor for later obesity, but it is unknown whether identification of other risk factors, including recently discovered genetic markers, would help to identify children at risk of developing adult obesity.Our objective was to examine the childhood environmental and genetic predictors of adult obesity.We followed 2119 individuals of the Cardiovascular Risk in Young Finns Study for up to 27 yr since baseline (1980, age 3-18 yr).We evaluated adult obesity [body mass index (BMI) ≥ 30 kg/m(2)].The independent predictors (P0.05) of adult obesity included childhood BMI, C-reactive pro…

Genome-wide association meta-analysis of PR interval identifies 47 novel loci associated with atrial and atrioventricular electrical activity

ABSTRACTElectrocardiographic PR interval measures atrial and atrioventricular depolarization and conduction, and abnormal PR interval is a risk factor for atrial fibrillation and heart block. We performed a genome-wide association study in over 92,000 individuals of European descent and identified 44 loci associated with PR interval (34 novel). Examination of the 44 loci revealed known and novel biological processes involved in cardiac atrial electrical activity, and genes in these loci were highly over-represented in several cardiac disease processes. Nearly half of the 61 independent index variants in the 44 loci were associated with atrial or blood transcript expression levels, or were i…

Relative age at school entry, school performance and long-term labour market outcomes

This article examines the impact of relative age at school entry on school performance, educational attainment and labour market outcomes later in life. We find that the advantages of maturity at school entry are short-lived with relative age having no impact on the years of formal education, adulthood earnings or employment. Our findings are consistent with the view that assumes modest maturity effects in countries where formal education begins late and there are no ability-differentiated learning groups at initial grades. peerReviewed

Biomarkers and Long-Term Labour Market Outcomes: The Case of Creatine

I evaluate the impact of the UK Working Time Regulations 1998, which introduced mandatory paid holiday entitlement. The regulation gave (nearly) all workers the right to a minimum of 4 weeks of paid holiday per a year. With constant weekly pay this change amounts effectively to an increase in the real hourly wage of about 8.5% for someone going from 0 to 4 weeks paid holiday per year, which should lead to adjustments in employment. For employees I use complementary log-log regression to account for right-censoring of employment spells. I find no increase in the hazard to exit employment within a year after treatment. Adjustments in wages cannot explain this result as they are increasing for…

Longitudinal physical activity trajectories from childhood to adulthood and their determinants : The Young Finns Study

Determining lifelong physical activity (PA) trajectories and their determinants is essential to promote a physically active lifestyle throughout the life-course. We aimed to identify PA trajectories from childhood to midlife and their determinants in a longitudinal population-based cohort. This study is a part of the Cardiovascular Risk in Young Finns Study. From 1980, a population-based cohort (N = 3596; 1764 boys/1832 girls, age 3-18 years) has been followed up for 31 years. PA indices were formed based on self-reported data (between age 9-49 years) on frequency, duration, and intensity of leisure (during childhood) or high-intensity (at later age) PA and on sports club participation/comp…

Association of maternal prenatal smoking GFI1-locus and cardio-metabolic phenotypes in 18,212 adults

Background: DNA methylation at the GFI1-locus has been repeatedly associated with exposure to smoking from the foetal period onwards. We explored whether DNA methylation may be a mechanism that links exposure to maternal prenatal smoking with offspring's adult cardio-metabolic health.Methods: We meta-analysed the association between DNA methylation at GFI1-locus with maternal prenatal smoking, adult own smoking, and cardio-metabolic phenotypes in 22 population-based studies from Europe, Australia, and USA (n= 18,212). DNA methylation at the GFI1-locus was measured in whole-blood. Multivariable regression models were fitted to examine its association with exposure to prenatal and own adult s…

Associations of partnering transition and socioeconomic status with a four-year change in daily steps among Finnish adults

Aim: The aim of this prospective four-year follow-up study was to examine how socioeconomic status (SES) and change in marital status are associated with the change in pedometer-measured physical activity (PA) in adulthood among participants in the ‘Cardiovascular Risk in Young Finns Study’. Methods: Questionnaires were completed and pedometers worn at baseline in 2007 and again at follow-up in 2011 by 1051 Finnish adults (62.3% female, aged 30–45 years in 2007). A latent change score model was used to examine mean change in daily total steps, aerobic steps and non-aerobic steps during weekdays and weekend days between 2007 and 2011. Results: In women re-coupling or finding a new partner wa…

Genome-wide associations for birth weight and correlations with adult disease

Birth weight (BW) has been shown to be influenced by both fetal and maternal factors and in observational studies is reproducibly associated with future risk of adult metabolic diseases including type 2 diabetes (T2D) and cardiovascular disease. These life-course associations have often been attributed to the impact of an adverse early life environment. Here, we performed a multi-ancestry genome-wide association study (GWAS) meta-analysis of BW in 153,781 individuals, identifying 60 loci where fetal genotype was associated with BW (P < 5 × 10(-8)). Overall, approximately 15% of variance in BW was captured by assays of fetal genetic variation. Using genet…

Birth weight and adult income : An examination of mediation through adult height and body mass

This paper examines the causal links between early human endowments and socioeconomic outcomes in adulthood. We use a genotyped longitudinal survey (Cardiovascular Risk in Young Finns Study) that is linked to the administrative registers of Statistics Finland. We focus on the effect of birth weight on income via two anthropometric mediators: body mass index (BMI) and height in adulthood. We find that (i) the genetic instruments for birth weight, adult height, and adult BMI are statistically powerful; (ii) there is a robust total effect of birth weight on income for men but not for women; (iii) the total effect of birth weight on income for men is partly mediated via height but not via BMI; …

Tracking and Changes in Daily Step Counts among Finnish Adults

Purpose This study aimed to investigate the tracking and changes of steps per day in adults and their determinants over 13 yr. Methods A total of 2195 subjects (1236 women) 30-45 yr of age were randomly recruited from the ongoing Cardiovascular Risk in Young Finns Study in 2007 and were followed up in 2020. Steps per day, including both total and aerobic steps per day, were monitored for seven consecutive days with a pedometer in 2007-2008 and 2011-2012 and with an accelerometer in 2018-2020. Tracking was analyzed using Spearman's correlation. Stability and changes of steps per day over time in both low-active and high-active groups (based on median values) were described by percentage agre…

Does Childhood Temperamental Activity Predict Physical Activity and Sedentary Behavior over a 30-Year Period? Evidence from the Young Finns Study

We examined associations between childhood temperamental activity, physical activity (PA), and television (TV) viewing over a 30-year period. The participants (1220 boys and 1237 girls) were aged 3, 6, 9, and 12 years in 1980 and were followed until 2011. Temperamental activity was evaluated by participants' mothers at baseline. The PA was assessed based on maternal ratings of the child from ages 3 to 6 and via self-report age from the age of 9 across all measurements. TV viewing was assessed using self-reports taken from 2001 to 2011. The associations between temperamental activity and the level and change of PA and TV viewing were determined using linear growth modeling stratified by gend…

Life-time risk factors and progression of carotid atherosclerosis in young adults: the Cardiovascular Risk in Young Finns study.

Aims The aim of this study is to evaluate whether childhood risk factors are associated with a 6-year change in carotid intima-media thickness (IMT) in young adulthood independent of the current risk factors. Methods and results The Cardiovascular Risk in Young Finns cohort consisted of 1809 subjects who were followed-up for 27 years since baseline (1980, age 3–18 years) and having carotid IMT measured both in 2001 and 2007. Cardiovascular risk factors were assessed repeatedly since childhood. A genotype risk score was calculated using 17 newly identified genetic variants associating with cardiovascular morbidity. The number of childhood risk factors (high LDL-cholesterol, low HDL-cholester…

Longitudinal associations between parental and offspring's leisure-time physical activity: The Young Finns Study.

Purpose The longitudinal influence of parental leisure-time physical activity (LTPA) on their offspring's LTPA is poorly understood. This study examined the longitudinal associations between parental LTPA and offspring's LTPA at two-time intervals. Method Child (offspring) participants (N=3596) were enrolled from the Cardiovascular Risk in Young Finns Study in 1980. Their LTPA was self-rated through nine phases from baseline to 2018 and categorized by year into youth (1980-1986) and adult (1992-2018) LTPA. Parental LTPA was assessed with a single self-reported question at three phases from 1980 to 1986. Latent growth curve modeling stratified by gender was fitted to estimate the potential p…

Effects of persistent physical activity and inactivity on coronary risk factors in children and young adults. The Cardiovascular Risk in Young Finns Study.

The tracking of physical activity and its influence on selected coronary heart disease risk factors were studied in a 6-year (original survey in 1980, with follow-ups in 1983 and 1986) study of Finnish adolescents and young adults as part of the Cardiovascular Risk in Young Finns Study. The subjects in this analysis were aged 12, 15, and 18 years at baseline. Physical activity was assessed with a standardized questionnaire, and a sum index was derived from the product of intensity, frequency, and duration of leisure time physical activity. Complete data on physical activity index from each study year were available on 961 participants. Significant tracking of physical activity was observed …

Common Genetic Variation in Relation to Brachial Vascular Dimensions and Flow-Mediated Vasodilation

Common Genetic Variation in Relation to Brachial Vascular Dimensions and Flow-Mediated Vasodilation

Repositioning of the global epicentre of non-optimal cholesterol

Publisher's version (útgefin grein)

Convergent Validity of a Physical Activity Questionnaire against Objectively Measured Physical Activity in Adults: The Cardiovascular Risk in Young Finns Study

Background: Traditionally, a self-reported questionnaire has been a cost-effective method of gathering information about physical activity (PA). An objective measurement, such as the use of a pedometer, can be used to validate the findings of a PA questionnaire in a large population. Objective: The study objective was to determine the convergent validity of a PA questionnaire against objectively measured PA in adults obtained with the use of a pedometer. Methods: Data from the Cardiovascular Risk in Young Finns Study (YFS) were collected from 1853 participants aged 30 - 45 years. The participants completed a self-reported questionnaire that included items on leisure time, commuting and habi…

Genome-wide association study for refractive astigmatism reveals genetic co-determination with spherical equivalent refractive error: the CREAM consortium

To identify genetic variants associated with refractive astigmatism in the general population, meta-analyses of genome-wide association studies were performed for: White Europeans aged at least 25 years (20 cohorts, N = 31,968); Asian subjects aged at least 25 years (7 cohorts, N = 9,295); White Europeans aged <25 years (4 cohorts, N = 5,640); and all independent individuals from the above three samples combined with a sample of Chinese subjects aged <25 years (N = 45,931). Participants were classified as cases with refractive astigmatism if the average cylinder power in their two eyes was at least 1.00 diopter and as controls otherwise. Genome-wide association analysis was carried out for …

Longitudinal associations between parental and offspring’s leisure‐time physical activity : The Young Finns Study

Purpose The longitudinal influence of parental leisure-time physical activity (LTPA) on their offspring’s LTPA is poorly understood. This study examined the longitudinal associations between parental LTPA and offspring’s LTPA at two-time intervals. Method Child (offspring) participants (N=3596) were enrolled from the Cardiovascular Risk in Young Finns Study in 1980. Their LTPA was self-rated through nine phases from baseline to 2018 and categorized by year into youth (1980‒1986) and adult (1992‒2018) LTPA. Parental LTPA was assessed with a single self-reported question at three phases from 1980 to 1986. Latent growth curve modeling stratified by gender was fitted to estimate the potential p…

Parental Physical Activity Associates With Offspring's Physical Activity Until Middle Age: A 30-Year Study.

Background:Parents’ physical activity associates with their children’s physical activity. Prospective designs assessing this association are rare. This study examined how parents’ physical activity was associated with their children’s physical activity from childhood to middle adulthood in a 30-year prospective, population-based setting.Methods:Participants (n = 3596) were from the ongoing Cardiovascular Risk in Young Finns study started in 1980. Participants’ physical activity was self-reported at 8 phases from 1980 to 2011, and their parents’ physical activity at 1980. Analyses were adjusted for a set of health-related covariates assessed from 1980 to 2007.Results:High levels of mothers’ …

Genetic determinants of heel bone properties: genome-wide association meta-analysis and replication in the GEFOS/GENOMOS consortium

Quantitative ultrasound of the heel captures heel bone properties that independently predict fracture risk and, with bone mineral density (BMD) assessed by X-ray (DXA), may be convenient alternatives for evaluating osteoporosis and fracture risk. We performed a meta-analysis of genome-wide association (GWA) studies to assess the genetic determinants of heel broadband ultrasound attenuation (BUA; n = 14 260), velocity of sound (VOS; n = 15 514) and BMD (n = 4566) in 13 discovery cohorts. Independent replication involved seven cohorts with GWA data (in silico n = 11 452) and new genotyping in 15 cohorts (de novo n = 24 902). In combined random effects, meta-analysis of the discovery and repli…

Physical Activity, Sleep, and Symptoms of Depression in Adults - Testing for Mediation

Abstract Purpose: Physical activity, sleep problems, and symptoms of depression contribute to overall well-being. The factors are reciprocally associated, but the nature of these associations remains unclear. The present study examined whether sleep problems mediated the association between physical activity and depressive symptoms. Methods: The eligible population (n = 3596) consisted of adults from the ongoing, population-based Cardiovascular Risk in Young Finns Study started in 1980. Participants’ leisure-time physical activity was assessed with physical activity index (2007) and sleep problems with Jenkins’ Sleep Questionnaire in 2007 and 2011. Depressive symptoms were measured using mo…

Associations of partnering transition and socioeconomic status with a four-year change in daily steps among Finnish adults.

Aim: The aim of this prospective four-year follow-up study was to examine how socioeconomic status (SES) and change in marital status are associated with the change in pedometer-measured physical activity (PA) in adulthood among participants in the ‘Cardiovascular Risk in Young Finns Study’. Methods: Questionnaires were completed and pedometers worn at baseline in 2007 and again at follow-up in 2011 by 1051 Finnish adults (62.3% female, aged 30–45 years in 2007). A latent change score model was used to examine mean change in daily total steps, aerobic steps and non-aerobic steps during weekdays and weekend days between 2007 and 2011. Results: In women re-coupling or finding a new partner wa…

Testing a model of physical activity and obesity tracking from youth to adulthood: the cardiovascular risk in young Finns study

To test a potential model of the relationship between physical activity and obesity from youth to adulthood.Longitudinal study data from the cardiovascular risk in young Finns study.A total of 1319 boys (n=626) and girls (n=693) aged 9, 12, 15 and 18 years were randomly selected from five university towns and their rural surroundings in 1980. They were followed up for 21 years. In 2001 they were 30, 33, 36 and 39 years old.Physical activity was assessed by a short questionnaire at two measurement points. Obesity was measured by body mass index (BMI) and sum of skinfolds in 1980 and BMI and waist circumference in 2001.Structural equation analysis (LISREL) indicated that the prevalence of abd…

Longitudinal Associations between Physical Activity and Educational Outcomes

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Associations Between Trajectories of Leisure-Time Physical Activity and Television Viewing Time Across Adulthood: The Cardiovascular Risk in Young Finns Study.

Background: The purpose of this study was to examine trajectories of leisure-time physical activity (LTPA) and television-viewing (TV) time and their associations in adults over 10 years. Methods: The sample comprised 2934 participants (men, 46.0%) aged 24–39 years in 2001 and they were followed up for 10 years. LTPA and TV time were assessed using self-report questionnaires in 2001, 2007, and 2011. Longitudinal LTPA and TV-time trajectories and their interactions were analyzed with mixture modeling. Results: Three LTPA (persistently highly active, 15.8%; persistently moderately active, 60.8%; and persistently low active, 23.5%) and 4 TV time (consistently low, 38.6%; consistently moderate,…

Smoking and Physical Activity Trajectories from Childhood to Midlife.

Introduction: Despite substantial interest in the development of health behaviors, there is limited research that has examined the longitudinal relationship between physical activity (PA) and smoking trajectories from youth to adulthood in a Finnish population. This study aimed to identify trajectories of smoking and PA for males and females, and study the relationship between these trajectories from youth to adulthood. Methods: Latent profile analysis (LPA) was used to identify trajectories of smoking and PA separately for males and females among 3355 Finnish adults (52.1% females). Participants&rsquo

Association of lifetime blood pressure with adulthood exercise blood pressure response: the cardiovascular risk in young Finns study

Elevated blood pressure (BP) in childhood has been associated with increased adulthood BP. However, BP and its change from childhood to adulthood and the risk of exaggerated adulthood exercise BP response are largely unknown. Therefore, we studied the association of childhood and adulthood BP with adulthood exercise BP response. This investigation consisted of 406 individuals participating in the ongoing Cardiovascular Risk in Young Finns Study (baseline in 1980, at age of 6–18 years; follow-up in adulthood in 27–29 years since baseline). In childhood BP was classified as elevated according to the tables from the International Child Blood Pressure References Establishment Consortium, while …

Personality, occupational sorting and routine work

PurposeA prominent labour market feature in recent decades has been the increase in abstract and service jobs, while the demand for routine work has declined. This article examines whether the components of Type A behaviour predict workers' selection into non-routine abstract, non-routine service and routine jobs.Design/methodology/approachBuilding on the work by Barrick et al. (2013), this article first presents how the theory of purposeful work behaviour can be used to explain how individuals with different levels of Type A components sort into abstract, service and routine jobs. Then, using longitudinal data, it examines whether the components of Type A behaviour predict occupational sor…

Physical Inactivity from Youth to Adulthood and Risk of Impaired Glucose Metabolism

Introduction: Physical activity (PA) is important in the prevention and treatment of impaired glucose metabolism. However, association of physical inactivity during the transition between childhood and adulthood with glucose metabolism is unknown. Therefore, we studied the association of persistent physical inactivity since childhood with glucose metabolism in adulthood. Methods: Data were drawn from the ongoing, Cardiovascular Risk in Young Finns Study with repeated follow-ups between 1980 and 2011 (baseline age, 3-18 yr; n = 3596). Impaired glucose metabolism was defined as having impaired fasting glucose (6.1-6.9 mmol·L-1) or type 2 diabetes in adulthood. Leisure-time PA habits were repe…

Genome-wide association studies identify 137 loci for DNA methylation biomarkers of ageing

AbstractBiological ageing estimators derived from DNA methylation (DNAm) data are heritable and correlate with morbidity and mortality. Leveraging DNAm and SNP data from &gt;41,000 individuals, we identify 137 genome-wide significant loci (113 novel) from meta-analyses of four epigenetic clocks and epigenetic surrogate markers for granulocyte proportions and plasminogen activator inhibitor 1 levels, respectively. We report strong genetic correlations with longevity and lifestyle factors such as smoking, education, and obesity. Significant associations are observed in polygenic risk score analysis and to a lesser extent in Mendelian randomization analyses. This study illuminates the genetic …

Genome Analyses of >200,000 Individuals Identify 58 Loci for Chronic Inflammation and Highlight Pathways that Link Inflammation and Complex Disorders

International audience; C-reactive protein (CRP) is a sensitive biomarker of chronic low-grade inflammation and is associated with multiple complex diseases. The genetic determinants of chronic inflammation remain largely unknown, and the causal role of CRP in several clinical outcomes is debated. We performed two genome-wide association studies (GWASs), on HapMap and 1000 Genomes imputed data, of circulating amounts of CRP by using data from 88 studies comprising 204,402 European individuals. Additionally, we performed in silico functional analyses and Mendelian randomization analyses with several clinical outcomes. The GWAS meta-analyses of CRP revealed 58 distinct genetic loci (p < 5 × 1…

Long-term Leisure-time Physical Activity and Serum Metabolome

Background— Long-term physical inactivity seems to cause many health problems. We studied whether persistent physical activity compared with inactivity has a global effect on serum metabolome toward reduced cardiometabolic disease risk. Methods and Results— Sixteen same-sex twin pairs (mean age, 60 years) were selected from a cohort of twin pairs on the basis of their &gt;30-year discordance for physical activity. Persistently (≥5 years) active and inactive groups in 3 population-based cohorts (mean ages, 31–52 years) were also studied (1037 age- and sex-matched pairs). Serum metabolome was quantified by nuclear magnetic resonance spectroscopy. We used permutation analysis to estimate the …

Association of lifetime blood pressure with adulthood exercise blood pressure response: the cardiovascular risk in young Finns study

Elevated blood pressure (BP) in childhood has been associated with increased adulthood BP. However, BP and its change from childhood to adulthood and the risk of exaggerated adulthood exercise BP response are largely unknown. Therefore, we studied the association of childhood and adulthood BP with adulthood exercise BP response. This investigation consisted of 406 individuals participating in the ongoing Cardiovascular Risk in Young Finns Study (baseline in 1980, at age of 6–18 years; follow-up in adulthood in 27–29 years since baseline). In childhood BP was classified as elevated according to the tables from the International Child Blood Pressure References Establishment Consortium, while …

Income and Physical Activity among Adults: Evidence from Self-Reported and Pedometer-Based Physical Activity Measurements

This study examined the relationship between income and physical activity by using three measures to illustrate daily physical activity: the self-reported physical activity index for leisure-time physical activity, pedometer-based total steps for overall daily physical activity, and pedometer-based aerobic steps that reflect continuous steps for more than 10 min at a time. The study population consisted of 753 adults from Finland (mean age 41.7 years; 64% women) who participated in 2011 in the follow-up of the ongoing Young Finns study. Ordinary least squares models were used to evaluate the associations between income and physical activity. The consistency of the results was explored by us…

Gene-environment interactions between education and body mass: Evidence from the UK and Finland

More education is associated with a lower body mass index (BMI) and likelihood of being overweight. However, since a large proportion of the variation in body mass is due to genetic makeup, it has been hypothesized that education may moderate the genetic risk. We estimate main associations between (i) education, (ii) genetic risk, and (iii) interactions between education and genetic risk on BMI and the probability of being overweight in the UK and Finland. The estimates show that education is negatively associated with BMI and overweightness, and genetic risk is positively associated. However, the interactions between education and genetic risk are small and statistically insignificant. pee…

Systemic vascular resistance predicts the development of hypertension: the cardiovascular risk in young Finns study

To study whether systemic hemodynamics, especially systemic vascular resistance, predicts the development of hypertension and improves the risk prediction of incident hypertension beyond common risk factors in the risk models in young adults.Typical risk factors for hypertension in the risk prediction models (systolic and diastolic blood pressure, parental history of hypertension, age, sex, body-mass index, smoking), laboratory values (high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, triglycerides, glucose, insulin, C-reactive protein), heart rate (HR), stroke index (SI), and systemic vascular resistance index (SVRI) calculated by whole-body impedance cardiography …

Meta-analysis of exome array data identifies six novel genetic loci for lung function

Background: Over 90 regions of the genome have been associated with lung function to date, many of which have also been implicated in chronic obstructive pulmonary disease. Methods: We carried out meta-analyses of exome array data and three lung function measures: forced expiratory volume in one second (FEV1), forced vital capacity (FVC) and the ratio of FEV1 to FVC (FEV1/FVC). These analyses by the SpiroMeta and CHARGE consortia included 60,749 individuals of European ancestry from 23 studies, and 7,721 individuals of African Ancestry from 5 studies in the discovery stage, with follow-up in up to 111,556 independent individuals. Results: We identified significant (P&lt;2·8x10-7) associatio…

Sedentary behaviours and obesity in adults: the Cardiovascular Risk in Young Finns Study

Objective Sedentary behaviour may contribute to the development of obesity. We investigated the relations between different types of sedentary behaviour and adiposity markers in a well-characterised adult population after controlling for a wide range of potential confounders. Design Cross-sectional study. Setting The Cardiovascular Risk in Young Finns Multicenter Study. Participants Sedentary time (TV viewing, computer time, reading, music/radio listening and other relaxation) was assessed with a questionnaire for 1084 women and 909 men aged 30–45 years. Other study variables included occupational and leisure-time physical activity, sleep duration, socioeconomic status, smoking, alcohol con…

Does education protect against depression? Evidence from the Young Finns Study using Mendelian randomization

Using participants (N = 1733) drawn from the nationally representative longitudinal Young Finns Study (YFS) we estimate the effect of education on depressive symptoms. In 2007, when the participants were between 30 and 45 years old, they reported their depressive symptoms using a revised version of Beck's Depression Inventory. Education was measured using register information on the highest completed level of education in 2007, which was converted to years of education. To identify a causal relationship between education and depressive symptoms we use an instrumental variables approach (Mendelian randomization, MR) with a genetic risk score as an instrument for years of education. The genet…

Genome-wide meta-analysis identifies 56 bone mineral density loci and reveals 14 loci associated with risk of fracture

Bone mineral density (BMD) is the most widely used predictor of fracture risk. We performed the largest meta-analysis to date on lumbar spine and femoral neck BMD, including 17 genome-wide association studies and 32,961 individuals of European and east Asian ancestry. We tested the top BMD-associated markers for replication in 50,933 independent subjects and for association with risk of low-trauma fracture in 31,016 individuals with a history of fracture (cases) and 102,444 controls. We identified 56 loci (32 new) associated with BMD at genome-wide significance (P &lt; 5 × 10 -8). Several of these factors cluster within the RANK-RANKL-OPG, mesenchymal stem cell differentiation, endochondral…

The Molecular Genetic Architecture of Self-Employment

Economic variables such as income, education, and occupation are known to affect mortality and morbidity, such as cardiovascular disease, and have also been shown to be partly heritable. However, very little is known about which genes influence economic variables, although these genes may have both a direct and an indirect effect on health. We report results from the first large-scale collaboration that studies the molecular genetic architecture of an economic variable-entrepreneurship-that was operationalized using self-employment, a widely-available proxy. Our results suggest that common SNPs when considered jointly explain about half of the narrow-sense heritability of self-employment es…

Patterns of intense physical activity among 15- to 30-year-old Finns

Previous studies have reported increasing trends in physical activity in the Finnish population. These reports have not, however, included the perspective of cardiorespiratory stress in adolescent and young adults. We examined the present patterns of physical activity among Finnish adolescents and young adults in 1992. We specifically assessed whether the young people experience the volume of physical activity that is believed to stress the cardiorespiratory system appropriately in order to increase the level of fitness. The subjects in the present study were participants of a large multicenter study of atherosclerosis precursors in children and young adults. Physical activity was measured …

Factors associated with six-year weight change in young and middle-aged adults in the Young Finns Study

Objective. To examine factors associated with weight change and obesity risk in young and middle-aged adults. Subjects/methods. The Young Finns Study with its 923 women and 792 men aged 24–39 years at baseline were followed for six years. Variables associated with the weight change were investigated with regression models. Results. The average weight change was 0.45 kg/year in women and 0.58 kg/year in men. In women, weight change was steady across all ages. In men, weight changes were more pronounced in younger age groups. In women (weight gain &gt; 2 kg, n = 490), medication for anxiety, low occupational status, high baseline BMI (body mass index), high intake of sweet beverages, high chi…

Depressive symptoms and long-term income: The Young Finns Study

Abstract Background Higher depressive symptoms have been associated with lower future income. However, studies examining this issue have had limited follow-up times and have used self-reported measures of income. Also, possible confounders or mediators have not been accounted. Methods 971 women and 738 men were selected from the ongoing prospective Young Finns Study (YFS) that began in 1980. Depressive symptoms were measured in 1992 when participants were from 15 to 30 years old. Information on annual income and earnings from 1993 to 2010 were obtained from the Finnish Longitudinal Employer-Employee Data (FLEED) of Statistics Finland and linked to the YFS. Results Higher depressive symptoms…

Active commuting from youth to adulthood and as a predictor of physical activity in early midlife: The Young Finns Study

Abstract Objective The aims of the study were to describe the stability of active commuting (AC) behavior (i.e., walking and cycling) over 27 years and examine the relationship between AC and physical activity (PA) from youth to early midlife. Methods The mode and distance of travel were assessed using a self-reported questionnaire at five consecutive measurements between 1980 and 2007, when 2072 individuals were followed up from youth (9–18 years) to adulthood (30–45 years). PA was also measured using a questionnaire. Results The prevalence of AC declined sharply with age, particularly after 12 years, while AC distances to work or place of study increased substantially. AC was concurrently…

Physical Inactivity from Youth to Adulthood and Risk of Impaired Glucose Metabolism

INTRODUCTION: Physical activity (PA) is important in the prevention and treatment of impaired glucose metabolism. However, association of physical inactivity during the transition between childhood and adulthood with glucose metabolism is unknown. Therefore, we studied the association of persistent physical inactivity since childhood with glucose metabolism in adulthood. METHODS: Data were drawn from the ongoing, Cardiovascular Risk in Young Finns Study with repeated follow-ups between 1980 and 2011 (baseline age, 3-18 yr; n = 3596). Impaired glucose metabolism was defined as having impaired fasting glucose (6.1-6.9 mmol·L) or type 2 diabetes in adulthood. Leisure-time PA habits were repeat…

Longitudinal physical activity trajectories from childhood to adulthood and their determinants: The Young Finns Study

Determining lifelong physical activity (PA) trajectories and their determinants is essential to promote a physically active lifestyle throughout the life-course. We aimed to identify PA trajectories from childhood to midlife and their determinants in a longitudinal population-based cohort. This study is a part of the Cardiovascular Risk in Young Finns Study. From 1980, a population-based cohort (N = 3596; 1764 boys/1832 girls, age 3-18 years) has been followed up for 31 years. PA indices were formed based on self-reported data (between age 9-49 years) on frequency, duration, and intensity of leisure (during childhood) or high-intensity (at later age) PA and on sports club participation/comp…

Creatine and entrepreneurship

Creatine is a nitrogenous organic acid which supplies energy to body cells and enhances physical performance. Using the Young Finns Study combined with the Finnish Linked employer-employee data we show that quantities of creatine measured in 1980 prior to labour market entry affect entrepreneurial success as measured by capital income accumulation over the period 1993–2010 (in particular for females). However, we do not find evidence that creatine affects the propensity to become an entrepreneur. Our study contributes to the emerging literature on biomarkers and entrepreneurship. peerReviewed

Maternal and fetal genetic contribution to gestational weight gain

Background: Clinical recommendations to limit gestational weight gain (GWG) imply high GWG is causally related to adverse outcomes in mother or offspring, but GWG is the sum of several inter-related complex phenotypes (maternal fat deposition and vascular expansion, placenta, amniotic fluid and fetal growth). Understanding the genetic contribution to GWG could help clarify the potential effect of its different components on maternal and offspring health. Here we explore the genetic contribution to total, early and late GWG. Participants and methods: A genome-wide association study was used to identify maternal and fetal variants contributing to GWG in up to 10 543 mothers and 16 317 offspri…

Large-scale genome-wide analysis identifies genetic variants associated with cardiac structure and function

BACKGROUND: Understanding the genetic architecture of cardiac structure and function may help to prevent and treat heart disease. This investigation sought to identify common genetic variations associated with inter-individual variability in cardiac structure and function. METHODS: A GWAS meta-analysis of echocardiographic traits was performed, including 46,533 individuals from 30 studies (EchoGen consortium). The analysis included 16 traits of left ventricular (LV) structure, and systolic and diastolic function. RESULTS: The discovery analysis included 21 cohorts for structural and systolic function traits (n = 32,212) and 17 cohorts for diastolic function traits (n = 21,852). Replication …

Factors associated with six-year weight change in young and middle-aged adults in the Young Finns Study.

To examine factors associated with weight change and obesity risk in young and middle-aged adults.The Young Finns Study with its 923 women and 792 men aged 24-39 years at baseline were followed for six years. Variables associated with the weight change were investigated with regression models.The average weight change was 0.45 kg/year in women and 0.58 kg/year in men. In women, weight change was steady across all ages. In men, weight changes were more pronounced in younger age groups. In women (weight gain2 kg, n = 490), medication for anxiety, low occupational status, high baseline BMI (body mass index), high intake of sweet beverages, high childhood BMI, high salt (NaCl and/or KCl) use, l…

The role of obesity and physical activity in non-specific and radiating low back pain: The Young Finns study

Objective To study the effects of obesity, physical activity, and change in physical activity on the incidence of low back pain and explore whether obesity modifies the effects of physical activity. Methods As part of the ongoing Young Finns Study, 1224 subjects aged 24–39 years free from low back pain during the preceding 12 months at baseline in 2001 were included. Obesity was defined based on the body mass index (BMI) and waist circumference, and physical activity was assessed by the metabolic equivalent of task (MET) index in 2001 and 2007. Results Abdominal obesity, defined by an increased waist circumference, was associated with an increased incidence of radiating low back pain (adjus…

The challenges of GxE research: A rejoinder

Association of lifetime blood pressure with adulthood exercise blood pressure response : the cardiovascular risk in young Finns study

Purpose: Elevated blood pressure (BP) in childhood has been associated with increased adulthood BP. However, BP and its change from childhood to adulthood and the risk of exaggerated adulthood exercise BP response are largely unknown. Therefore, we studied the association of childhood and adulthood BP with adulthood exercise BP response. Materials and methods: This investigation consisted of 406 individuals participating in the ongoing Cardiovascular Risk in Young Finns Study (baseline in 1980, at age of 6–18 years; follow-up in adulthood in 27–29 years since baseline). In childhood BP was classified as elevated according to the tables from the International Child Blood Pressure References …

Genetic associations at 53 loci highlight cell types and biological pathways relevant for kidney function

Reduced glomerular filtration rate defines chronic kidney disease and is associated with cardiovascular and all-cause mortality. We conducted a meta-analysis of genome-wide association studies for estimated glomerular filtration rate (eGFR), combining data across 133,413 individuals with replication in up to 42,166 individuals. We identify 24 new and confirm 29 previously identified loci. Of these 53 loci, 19 associate with eGFR among individuals with diabetes. Using bioinformatics, we show that identified genes at eGFR loci are enriched for expression in kidney tissues and in pathways relevant for kidney development and transmembrane transporter activity, kidney structure, and regulation o…

Changes in Daily Steps and Body Mass Index and Waist to Height Ratio during Four Year Follow-Up in Adults: Cardiovascular Risk in Young Finns Study

Aims: Over the study years, there was a significant increase in body mass index (BMI) and waist-to-height ratio (WtHR) in middle aged Finnish adults. Methods: Data were obtained from 1033 Finnish adults from the Cardiovascular Risk in Young Finns Study in 2007 and 2011. Cohort study participants wore an Omron Walking Style One (HJ-152R-E) pedometer for five days and were grouped into those who increased, maintained and decreased their steps between 2007 and 2011. Paired samples t-test was used to compare body mass index (BMI) and waist-to-height ratio (WtHR) change values between the change groups in study years. Results: Among study population BMI and WtHR increase between study years was …

Evaluation of Shared Genetic Susceptibility to High and Low Myopia and Hyperopia

Importance: Uncertainty currently exists about whether the same genetic variants are associated with susceptibility to low myopia (LM) and high myopia (HM) and to myopia and hyperopia. Addressing this question is fundamental to understanding the genetics of refractive error and has clinical relevance for genotype-based prediction of children at risk for HM and for identification of new therapeutic targets. Objective: To assess whether a common set of genetic variants are associated with susceptibility to HM, LM, and hyperopia. Design, Setting, and Participants: This genetic association study assessed unrelated UK Biobank participants 40 to 69 years of age of European and Asian ancestry. Par…

Is It Good To Be Good? Dispositional Compassion and Health Behaviors

Background Despite the documented importance of dispositional compassions for a range of health-related outcomes, its role in predicting health behaviors remains unclear. Purpose This study examined the associations between dispositional compassion and three domains of health behavior, including physical activity, alcohol use, and smoking. Methods The participants (N = 1,279–1,913) were from the Finnish population-based Young Finns study. We collected self-reports of compassion in 1997 and 2011 and health behaviors in 2001, 2007, and 2011. In addition, an objective pedometer measure of physical activity was collected in 2011. Linear and logistic regression models were fitted to estimate the…

Life-course leisure-time physical activity trajectories in relation to health-related behaviors in adulthood: the Cardiovascular Risk in Young Finns study

Background Evidence on whether leisure-time physical activity (LTPA) facilitates individuals’ adoption of multiple healthy behaviors remains scarce. This study investigated the associations of diverse longitudinal LTPA trajectories from childhood to adulthood with diet, screen time, smoking, binge drinking, sleep difficulties, and sleep duration in adulthood. Methods Data were drawn from the Cardiovascular Risk in Young Finns Study. Participants were aged 9–18 years (N = 3553; 51% females) in 1980 and 33–49 years at the latest follow-up in 2011. The LTPA trajectories were identified using a latent profile analysis. Differences in self-reported health-related behaviors across the LTPA trajec…

High Intestinal Cholesterol Absorption Is Associated With Cardiovascular Disease and Risk Alleles in ABCG8 and ABO

Objectives This study sought to determine whether high intestinal cholesterol absorption represents a cardiovascular risk factor and to link ABCG8 and ABO variants to cardiovascular disease (CVD). Background Plant sterol–enriched functional foods are widely used for cholesterol lowering. Their regular intake yields a 2-fold increase in circulating plant sterol levels that equally represent markers of cholesterol absorption. Variants in ABCG8 and ABO have been associated with circulating plant sterol levels and CVD, thereby suggesting atherogenic effects of plant sterols or of cholesterol uptake. Methods The cholestanol-to-cholesterol ratio (CR) was used as an estimate of cholesterol absorpt…

Variants associated with HHIP expression have sex-differential effects on lung function

Background: Lung function is highly heritable and differs between the sexes throughout life. However, little is known about sex-differential genetic effects on lung function. We aimed to conduct the first genome-wide genotype-by-sex interaction study on lung function to identify genetic effects that differ between males and females. Methods: We tested for interactions between 7,745,864 variants and sex on spirometry-based measures of lung function in UK Biobank (N=303,612), and sought replication in 75,696 independent individuals from the SpiroMeta consortium. Results: Five independent single-nucleotide polymorphisms (SNPs) showed genome-wide significant (P&lt;5x10-8) interactions with sex …

Trajectories of Physical Activity Predict the Onset of Depressive Symptoms but Not Their Progression: A Prospective Cohort Study

This prospective, community-based study examined trajectories of physical activity from childhood to adulthood and whether these trajectories contributed to depressive symptoms in adulthood to a greater degree than adulthood physical activity. Participants (n=3596) were from the ongoing Cardiovascular Risk in Young Finns Study which started in 1980. Depressive symptoms were measured with Beck Depression Inventory (BDI-II) in 2012, and physical activity was assessed from 1980 to 2011 with self-reports. Analyses were adjusted for age, sex, childhood negative emotionality, socioeconomic factors, previous depressive symptoms, social support, body mass index, and smoking status (1980–2007). High…

Physical Activity from Childhood to Adulthood and Cognitive Performance in Midlife

Introduction: Physical activity (PA) has been suggested to protect against old-age cognitive deficits. However, the independent role of childhood/youth PA for adulthood cognitive performance is unknown. This study investigated the association between PA from childhood to adulthood and midlife cognitive performance. Methods: This study is a part of the Cardiovascular Risk in Young Finns Study. Since 1980, a population-based cohort of 3596 children (age, 3–18 yr) have been followed up in 3- to 9-yr intervals. PA has been queried in all study phases. Cumulative PA was determined in childhood (age, 6–12 yr), adolescence (age, 12–18 yr), young adulthood (age, 18–24 yr), and adulthood (age, 24–37…

Tracking of physical activity from early childhood through youth into adulthood.

The aim of the study was to investigate the tracking of physical activity (PA) from preschool age to adulthood in six age cohorts of males and females.A random sample of 3596 boys and girls age 3-18 yr participated in the Cardiovascular Risks in Young Finns Study in 1980. The follow-up measurements were repeated in 1986, 1992, 2001, and 2007. The PA was measured by mother's report in 3- and 6-yr-olds and self-report in 9-yr-olds and older. Tracking of PA was analyzed using the Spearman rank-order correlation and a simplex model.Mother-reported PA at age 3 and 6 yr significantly predicted self-reported PA in youth and in young adulthood, and there was a significant indirect effect of mother …

Lifestyle Risk Factors Increase the Risk of Hospitalization for Sciatica: Findings of Four Prospective Cohort Studies

BACKGROUND: The purpose of this study is to assess the effects of lifestyle risk factors on the risk of hospitalization for sciatica and to determine whether overweight or obesity modifies the effect of leisure-time physical activity on hospitalization for sciatica. METHODS: We included 4 Finnish prospective cohort studies (Health 2000 Survey, Mobile Clinic Survey, Helsinki Health Study, and Young Finns Study) consisting of 34,589 participants and 1259 hospitalizations for sciatica during 12 to 30 years of follow-up. Sciatica was based on hospital discharge register data. We conducted a random-effects individual participant data meta-analysis. RESULTS: After adjustment for confounding facto…

Influence of early life risk factors and lifestyle on systemic vascular resistance in later adulthood: the cardiovascular risk in young Finns study

There are limited data available concerning the effects of lifetime risk factors and lifestyle on systemic hemodynamics, especially on systemic vascular resistance. The purpose of the study was to evaluate how lifetime cardiovascular risk factors (body mass index (BMI), high-density lipoprotein, low-density lipoprotein, triglycerides, systolic blood pressure, blood glucose) and lifestyle factors (vegetable consumption, fruit consumption, smoking and physical activity) predict systemic vascular resistance index (SVRI) and cardiac index (CI) assessed in adulthood. Our study cohort comprised 1635 subjects of the Cardiovascular Risk in Young Finns Study followed up for 27 years since baseline (…