Search results for "Mendelian Randomization"

Causal relationship of hepatic fat with liver damage and insulin resistance in nonalcoholic fatty liver

2017

Abstract Background and Aims Nonalcoholic fatty liver disease is epidemiologically associated with hepatic and metabolic disorders. The aim of this study was to examine whether hepatic fat accumulation has a causal role in determining liver damage and insulin resistance. Methods We performed a Mendelian randomization analysis using risk alleles in PNPLA3, TM6SF2, GCKR and MBOAT7, and a polygenic risk score for hepatic fat, as instruments. We evaluated complementary cohorts of at‐risk individuals and individuals from the general population: 1515 from the liver biopsy cohort (LBC), 3329 from the Swedish Obese Subjects Study (SOS) and 4570 from the population‐based Dallas Heart Study (DHS). Re…

Does higher education protect against obesity? Evidence using Mendelian randomization

2017

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 …

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

2019

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…

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

2021

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; …

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

2021

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…

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

2019

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…

P5313The association between coffee and caffeine consumption and renal function: insight from individual-level data, Mendelian randomization, and met…

2019

Abstract Background The reported relationship between coffee intake and renal function is poorly understood. Purpose By applying on two-sample Mendelian randomization (MR) and systematic review and meta-analysis we investigated the association between caffeine and coffee intake with prevalent CKD and markers of renal function. Methods For the individual data analysis we analysed the NHANES data on renal function markers and caffeine intake. MR was implemented by using summary-level data from genome-wide association studies conducted on coffee intake (N=91,462) and kidney function (N=133,413). Inverse variance weighted method (IVW), weighted median-based method, MR-Egger, MR-RAPS, MR-PRESSO …

Exposure to non-essential metals and albuminuria: exploring causal associations under a Mendelian randomization framework

2021

Plasma HDL cholesterol and risk of myocardial infarction: a mendelian randomisation study

2012

BACKGROUND: High plasma HDL cholesterol is associated with reduced risk of myocardial infarction, but whether this association is causal is unclear. Exploiting the fact that genotypes are randomly assigned at meiosis, are independent of non-genetic confounding, and are unmodified by disease processes, mendelian randomisation can be used to test the hypothesis that the association of a plasma biomarker with disease is causal. METHODS: We performed two mendelian randomisation analyses. First, we used as an instrument a single nucleotide polymorphism (SNP) in the endothelial lipase gene (LIPG Asn396Ser) and tested this SNP in 20 studies (20,913 myocardial infarction cases, 95,407 controls). Se…

Unraveling the relationship of loneliness and isolation in schizophrenia: Polygenic dissection and causal inference

2020

ABSTRACTThere is increasing recognition of the association between loneliness and social isolation (LNL-ISO) with schizophrenia. Here, we demonstrate significant LNL-ISO polygenic score prediction on schizophrenia in an independent case-control sample (N=3,488). We then dissect schizophrenia predisposing variation into subsets of variants based on their effect on LNL-ISO. Genetic variation with concordant effects in both phenotypes show significant SNP-based heritability enrichment, higher polygenic predictive ability in females and positive covariance with other mental disorders such as depression, anxiety, attention-deficit hyperactivity, alcohol use disorder, and autism. Conversely, gene…