A genome-wide association study of monozygotic twin-pairs suggests a locus related to variability of serum high-density lipoprotein cholesterol
Serum lipid levels have been associated with cardiovascular diseases, metabolic syndrome and type II diabetes (Kannel et al., 1961; Miller & Miller, 1975; Pilia et al., 2006). Variation in lipids levels is highly influenced by heritable factors (Friedlander et al., 1997) and 95 loci have already been associated with levels of high density lipoprotein (HDL) cholesterol, low density lipoprotein (LDL) cholesterol, triglycerides (TG) and total cholesterol (TC) in numerous study samples and replicated in various populations using genome-wide approaches (Aulchenko et al., 2008; Kathiresan et al., 2008; Kooner et al., 2008; Teslovich et al., 2010; Willer et al., 2008). However, the genetic associa…
Associations between sports participation, cardiorespiratory fitness, and adiposity in young adult twins.
Exercise behavior, cardiorespiratory fitness, and obesity are strongly influenced by genetic factors. By studying young adult twins, we examined to what extent these interrelated traits have shared genetic and environmental etiologies. We studied 304 twin individuals selected from the population-based FinnTwin16 study. Physical activity was assessed with the Baecke questionnaire, yielding three indexes: sport index, leisure-time index, and work index. In this study, we focused on sport index, which describes sports participation. Body composition was determined using dual-energy X-ray absorptiometry and cardiorespiratory fitness using a bicycle ergometer exercise test with gas exchange ana…
Genome-wide Association Analysis in Humans Links Nucleotide Metabolism to Leukocyte Telomere Length
Leukocyte telomere length (LTL) is a heritable biomarker of genomic aging. In this study, we perform a genome-wide meta-analysis of LTL by pooling densely genotyped and imputed association results across large-scale European-descent studies including up to 78,592 individuals. We identify 49 genomic regions at a false dicovery rate (FDR) < 0.05 threshold and prioritize genes at 31, with five highlighting nucleotide metabolism as an important regulator of LTL. We report six genome-wide significant loci in or near SENP7, MOB1B, CARMIL1, PRRC2A, TERF2, and RFWD3, and our results support recently identified PARP1, POT1, ATM, and MPHOSPH6 loci. Phenome-wide analyses in >350,000 UK Biobank p…
SNPs associated withHHIPexpression have differential effects on lung function in males and females
AbstractAdult lung function is highly heritable and 279 genetic loci were recently reported as associated with spirometry-based measures of lung function. Though lung development and function differ between males and females throughout life, there has been no genome-wide study to identify genetic variants with differential effects on lung function in males and females. Here, we present the first genome-wide genotype-by-sex interaction study on four lung function traits in 303,612 participants from the UK Biobank. We detected five SNPs showing genome-wide significant (P<5 × 10−8) interactions with sex on lung function, as well as 21 suggestively significant interactions (P<1 × 10−6). T…
Mitochondrial bioenergetic pathways in blood leukocyte transcriptome decrease after intensive weight loss but are rescued following weight regain in female physique athletes
Prolonged periods of energy deficit leading to weight loss induce metabolic adaptations resulting in reduced energy expenditure, but the mechanisms for energy conservation are incompletely understood. We examined 42 healthy athletic females (age 27.5 +/- 4.0 years, body mass index 23.4 +/- 1.7 kg/m(2)) who volunteered into either a group dieting for physique competition (n = 25) or a control group (n = 17). The diet group substantially reduced their energy intake and moderately increased exercise levels to induce loss of fat mass that was regained during a voluntary weight regain period. The control group maintained their typical lifestyle habits and body mass as instructed. From the diet g…
Telomere Length in Circulating Leukocytes is Associated with Lung Function and Disease
Several clinical studies suggest the involvement of premature ageing processes in chronic obstructive pulmonary disease (COPD). Using an epidemiological approach, we studied whether accelerated ageing indicated by telomere length, a marker of biological age, is associated with COPD and asthma, and whether intrinsic age-related processes contribute to the interindividual variability of lung function. Our meta-analysis of 14 studies included 934 COPD cases with 15 846 controls defined according to the Global Lungs Initiative (GLI) criteria (or 1189 COPD cases according to the Global Initiative for Chronic Obstructive Lung Disease (GOLD) criteria), 2834 asthma cases with 28 195 controls, and s…
Effects of 32-year leisure time physical activity discordance in twin pairs on health (TWINACTIVE study): aims, design and results for physical fitness.
AbstractThe physically active lifestyle is associated with low future morbidity and mortality, but the causality between physical activity and health is not always clear. As some inherited biological characteristics and childhood experiences may cause selection bias in observational studies, we sought to take them into account by identifying 16 twin pairs (7 MZ, 9 DZ, mean age 60 years) discordant for leisure time physical activity habits for thirty years. We conducted detailed health-related examinations among these twin pairs. Our main aims were to study the effects of physical activity and genes on fitness and body composition, with special reference to body fat compartments, metabolic s…
Persistence or Change in Leisure-Time Physical Activity Habits and Waist Gain During Early Adulthood: A Twin-Study
Objective To determine the relationship between persistence or change in leisure‐time physical activity habits and waist gain among young adults. Methods Population‐based cohort study among 3383 Finnish twin individuals (1578 men) from five birth cohorts (1975‐1979), who answered questionnaires at mean ages of 24.4 y (SD 0.9) and 33.9 y (SD 1.2), with reported self‐measured waist circumference. Persistence or change in leisure‐time physical activity habits was defined based on thirds of activity metabolic equivalent h/day during follow‐up (mean 9.5 y; SD 0.7). Results Decreased activity was linked to greater waist gain compared to increased activity (3.6 cm, P < 0.001 for men; 3.1 cm, P < 0…
Genetic architecture of circulating lipid levels
Serum concentrations of low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), triglycerides (TGs) and total cholesterol (TC) are important heritable risk factors for cardiovascular disease. Although genome-wide association studies (GWASs) of circulating lipid levels have identified numerous loci, a substantial portion of the heritability of these traits remains unexplained. Evidence of unexplained genetic variance can be detected by combining multiple independent markers into additive genetic risk scores. Such polygenic scores, constructed using results from the ENGAGE Consortium GWAS on serum lipids, were applied to predict lipid levels in an independen…
Daily energy expenditure through the human life course
Total daily energy expenditure (“total expenditure”, MJ/d) reflects daily energy needs and is a critical variable in human health and physiology, yet it is unclear how daily expenditure changes over the life course. Here, we analyze a large, globally diverse database of total expenditure measured by the doubly labeled water method for males and females aged 8 days to 95 yr. We show that total expenditure is strongly related to fat free mass in a power-law manner and identify four distinct metabolic life stages. Fat free mass-adjusted daily expenditure accelerates rapidly in neonates (0-1yr) to ~46% above adult values at ~1 yr, declines slowly throughout childhood and adolescence (1-20 yr) t…
Development of a Food-Based Diet Quality Score from a Short FFQ and Associations with Obesity Measures, Eating Styles and Nutrient Intakes in Finnish Twins
We constructed a food-based diet quality score (DQS) and examined its association with obesity measures, eating styles and nutrient intakes. Participants were 3592 individuals (764 dizygotic [DZ] and 430 monozygotic [MZ] twin pairs) from the FinnTwin16 study. The DQS (0&ndash
Variability in energy expenditure is much greater in males than females
In mammals, trait variation is often reported to be greater among males than females. However, to date, mainly only morphological traits have been studied. Energy expenditure represents the metabolic costs of multiple physical, physiological, and behavioral traits. Energy expenditure could exhibit particularly high greater male variation through a cumulative effect if those traits mostly exhibit greater male variation, or a lack of greater male variation if many of them do not. Sex differences in energy expenditure variation have been little explored. We analyzed a large database on energy expenditure in adult humans (1494 males and 3108 females) to investigate whether humans have evolved s…
Variation in human water turnover associated with environmental and lifestyle factors
Water is essential for survival, but one in three individuals worldwide (2.2 billion people) lacks access to safe drinking water. Water intake requirements largely reflect water turnover (WT), the water used by the body each day. We investigated the determinants of human WT in 5604 people from the ages of 8 days to 96 years from 23 countries using isotope-tracking ( 2 H) methods. Age, body size, and composition were significantly associated with WT, as were physical activity, athletic status, pregnancy, socioeconomic status, and environmental characteristics (latitude, altitude, air temperature, and humidity). People who lived in countries with a low human development index (HDI) had highe…
Genome-wide association and large-scale follow up identifies 16 new loci influencing lung function
Pulmonary function measures reflect respiratory health and are used in the diagnosis of chronic obstructive pulmonary disease. We tested genome-wide association with forced expiratory volume in 1 second and the ratio of forced expiratory volume in 1 second to forced vital capacity in 48,201 individuals of European ancestry with follow up of the top associations in up to an additional 46,411 individuals. We identified new regions showing association (combined P < 5 x 10(-8)) with pulmonary function in or near MFAP2, TGFB2, HDAC4, RARB, MECOM (also known as EVI1), SPATA9, ARMC2, NCR3, ZKSCAN3, CDC123, C10orf11, LRP1, CCDC38, MMP15, CFDP1 and KCNE2. Identification of these 16 new loci may p…
Leisure-time physical activity and high-risk fat: a longitudinal population-based twin study.
Exercise is thought to reduce high-risk body fat, but intervention studies are frequently limited by short follow-ups and observational studies by genetic selection. Therefore, we studied the effects of a physically inactive vs active lifestyle on high-risk (visceral, liver and intramuscular) fat in twin pairs discordant for leisure-time physical activity habits for over 30 years.A longitudinal population-based twin study.Sixteen middle-aged (50-74 years) same-sex twin pairs (seven monozygotic (MZ), nine dizygotic (DZ)) with long-term discordance for physical activity habits were comprehensively identified from the Finnish Twin Cohort (TWINACTIVE study). Discordance was initially defined in…
Additional file 1 of Blood and skeletal muscle ageing determined by epigenetic clocks and their associations with physical activity and functioning
Additional file 1: Within-pair correlations in age acceleration in blood and in muscle. Additional file 2: Associations between DNAmAge age acceleration estimates and body composition and physical activity in blood. Additional file 3: Sensitivity analyses related to twin pair discordance in body mass index.
Additional file 1 of Blood and skeletal muscle ageing determined by epigenetic clocks and their associations with physical activity and functioning
Additional file 1: Within-pair correlations in age acceleration in blood and in muscle. Additional file 2: Associations between DNAmAge age acceleration estimates and body composition and physical activity in blood. Additional file 3: Sensitivity analyses related to twin pair discordance in body mass index.
FinnTwin16 : A Longitudinal Study from Age 16 of a Population-Based Finnish Twin Cohort
The purpose of this review is to provide a detailed and updated description of the FinnTwin16 (FT16) study and its future directions. The Finnish Twin Cohort comprises three different cohorts: the Older Twin Cohort established in the 1970s and the FinnTwin12 and FT16 initiated in the 1990s. FT16 was initiated in 1991 to identify the genetic and environmental precursors of alcoholism, but later the scope of the project expanded to studying the determinants of various health-related behaviors and diseases in different stages of life. The main areas addressed are alcohol use and its consequences, smoking, physical activity, overall physical health, eating behaviors and eating disorders, weight…
Leisure-time physical activity and nutrition: a twin study
AbstractObjectiveTo determine the association between long-term leisure-time physical activity/inactivity and eating behaviours in twin pairs discordant for physical activity for 30 years.DesignCo-twin control design with cross-sectional data collection using questionnaire on eating habits and 5 d food diary. Differences in eating behaviours between physically active and inactive co-twins were analysed with pairwise tests.SettingFinland.SubjectsSixteen same-sex twin pairs (seven monozygotic and nine dizygotic, mean age 60 years) discordant for physical activity, selected from the Finnish Twin Cohort on the basis of physical activity discordance for 30 years, blinded to their possible differ…
FinnTwin16: A Longitudinal Study from Age 16 of a Population-Based Finnish Twin Cohort
AbstractThe purpose of this review is to provide a detailed and updated description of the FinnTwin16 (FT16) study and its future directions. The Finnish Twin Cohort comprises three different cohorts: the Older Twin Cohort established in the 1970s and the FinnTwin12 and FT16 initiated in the 1990s. FT16 was initiated in 1991 to identify the genetic and environmental precursors of alcoholism, but later the scope of the project expanded to studying the determinants of various health-related behaviors and diseases in different stages of life. The main areas addressed are alcohol use and its consequences, smoking, physical activity, overall physical health, eating behaviors and eating disorders…
Nicotinamide riboside improves muscle mitochondrial biogenesis, satellite cell differentiation, and gut microbiota in a twin study
Nicotinamide adenine dinucleotide (NAD + ) precursor nicotinamide riboside (NR) has emerged as a promising compound to improve obesity-associated mitochondrial dysfunction and metabolic syndrome in mice. However, most short-term clinical trials conducted so far have not reported positive outcomes. Therefore, we aimed to determine whether long-term NR supplementation boosts mitochondrial biogenesis and metabolic health in humans. Twenty body mass index (BMI)–discordant monozygotic twin pairs were supplemented with an escalating dose of NR (250 to 1000 mg/day) for 5 months. NR improved systemic NAD + metabolism, muscle mitochondrial number, myoblast differentiation, and gut microbiota compos…
Liver Fat, Adipose Tissue, and Body Composition Changes After Switching from a Protease Inhibitor or Efavirenz to Raltegravir.
Integrase inhibitors appear to increase body weight, but paradoxically some data indicate that raltegravir (RAL) may decrease liver fat. Our objective was to study the effects of switching from a protease inhibitor (PI) or efavirenz (EFV) to RAL on liver fat, body composition, and metabolic parameters among people living with HIV (PLWH) with high risk for nonalcoholic fatty liver disease (NAFLD). We randomized overweight PLWH with signs of metabolic syndrome to switch a PI or EFV to RAL (
Energy compensation and adiposity in humans
Publisher Copyright: © 2021 The Authors Understanding the impacts of activity on energy balance is crucial. Increasing levels of activity may bring diminishing returns in energy expenditure because of compensatory responses in non-activity energy expenditures.1–3 This suggestion has profound implications for both the evolution of metabolism and human health. It implies that a long-term increase in activity does not directly translate into an increase in total energy expenditure (TEE) because other components of TEE may decrease in response—energy compensation. We used the largest dataset compiled on adult TEE and basal energy expenditure (BEE) (n = 1,754) of people living normal lives to fi…
Identification of Gut Microbial Lysine and Histidine Degradation and CYP-Dependent Metabolites as Biomarkers of Fatty Liver Disease
Numerous studies have described specific metabolites as biomarkers ofsevere liver diseases, but very few have measured gut microbiota (GM)-produced metab-olites in fatty liver disease. We aimed atfinding GM signatures and metabolite markersin plasma and feces related to high liver fat content. Based on imaging, we dividedstudy participants into low (,5%, LF,n= 25) and high (.5%, HF,n= 39) liver fatgroups. Fecal (LFn= 14, HFn= 25) and plasma (LFn= 11, HFn= 7) metabolomes ofsubsets of participants were studied using liquid chromatography/high resolution massspectrometry. The GM were analyzed using 16S rRNA gene sequencing. Additionally,blood clinical variables and diet were studied. Dyslipide…
Persistence or change in leisure-time physical activity habits and waist gain during early adulthood: A twin-study
Objective To determine the relationship between persistence or change in leisure-time physical activity habits and waist gain among young adults. Methods Population-based cohort study among 3383 Finnish twin individuals (1578 men) from five birth cohorts (1975-1979), who answered questionnaires at mean ages of 24.4 y (SD 0.9) and 33.9 y (SD 1.2), with reported self-measured waist circumference. Persistence or change in leisure-time physical activity habits was defined based on thirds of activity metabolic equivalent h/day during follow-up (mean 9.5 y; SD 0.7). Results Decreased activity was linked to greater waist gain compared to increased activity (3.6 cm, P < 0.001 for men; 3.1 cm, P < 0…
A standard calculation methodology for human doubly labeled water studies.
Summary The doubly labeled water (DLW) method measures total energy expenditure (TEE) in free-living subjects. Several equations are used to convert isotopic data into TEE. Using the International Atomic Energy Agency (IAEA) DLW database (5,756 measurements of adults and children), we show considerable variability is introduced by different equations. The estimated rCO2 is sensitive to the dilution space ratio (DSR) of the two isotopes. Based on performance in validation studies, we propose a new equation based on a new estimate of the mean DSR. The DSR is lower at low body masses (<10 kg). Using data for 1,021 babies and infants, we show that the DSR varies non-linearly with body mass betw…
Physical inactivity and obesity: A vicious circle.
OBJECTIVE: Physical activity (PA) begins to decline in adolescence with a concomitant increase in weight. We hypothesized that a vicious circle may arise between decreasing PA and weight gain from adolescence to early adulthood. METHODS AND PROCEDURES: PA and self-perceived physical fitness assessed in adolescents (16-18 years of age) were used to predict the development of obesity (BMI > or =30 kg/m(2)) and abdominal obesity (waist >/=88 cm in females and > or =102 cm in males) at age 25 in 4,240 twin individuals (90% of twins born in Finland, 1975-1979). Ten 25-year-old monozygotic (MZ) twin pairs who were discordant for obesity (with a 16 kg weight difference) were then carefull…
Genome-wide association analysis identifies six new loci associated with forced vital capacity
Forced vital capacity (FVC), a spirometric measure of pulmonary function, reflects lung volume and is used to diagnose and monitor lung diseases. We performed genome-wide association study meta-analysis of FVC in 52,253 individuals from 26 studies and followed up the top associations in 32,917 additional individuals of European ancestry. We found six new regions associated at genome-wide significance (P <5 x 10(-8)) with FVC in or near EFEMP1, BMP6, MIR129-2-HSD17B12, PRDM11, WWOX and KCNJ2. Two loci previously associated with spirometric measures (GSTCD and PTCH1) were related to FVC. Newly implicated regions were followed up in samples from African-American, Korean, Chinese and Hispani…
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<5x10-8) interactions with sex …
Blood and skeletal muscle ageing determined by epigenetic clocks and their associations with physical activity and functioning
AbstractThe aim of this study was to investigate the correspondence of different biological ageing estimates (i.e. epigenetic age) in blood and muscle tissue and their associations with physical activity (PA), physical function and body composition. Two independent cohorts (N = 139 and N = 47) were included, whose age span covered adulthood (23–69 years). Whole blood and m. vastus lateralis samples were collected, and DNA methylation was analysed. Four different DNA methylation age (DNAmAge) estimates were calculated using genome-wide methylation data and publicly available online tools. A novel muscle-specific methylation age was estimated using the R-package ‘MEAT’. PA was measured with q…