Search results for "Mendelian Randomization"

Mapping risk factors for depression across the lifespan: An umbrella review of evidence from meta-analyses and Mendelian randomization studies

2018

The development of depression may involve a complex interplay of environmental and genetic risk factors. PubMed and PsycInfo databases were searched from inception through August 3, 2017, to identify meta-analyses and Mendelian randomization (MR) studies of environmental risk factors associated with depression. For each eligible meta-analysis, we estimated the summary effect size and its 95% confidence interval (CI) by random-effects modeling, the 95% prediction interval, heterogeneity with I 2 , and evidence of small-study effects and excess significance bias. Seventy meta-analytic reviews met the eligibility criteria and provided 134 meta-analyses for associations from 1283 primary studie…

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

2020

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…

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

2019

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…

The effects of age at menarche and first sexual intercourse on reproductive and behavioural outcomes:A Mendelian randomization study

2020

SummaryThere is substantial variation in the timing of significant reproductive life events such as menarche and first sexual intercourse. Life history theory explains this variation as an adaptive response to the developmental environment. In environments characterized by harsh conditions, adopting a fast life history strategy may increase fitness. In line with this, there is evidence demonstrating that greater childhood adversity is associated with earlier age at menarche. Here we applied Mendelian randomization (MR) methods to investigate whether there is a causal effect of variation in age at menarche and age at first sexual intercourse on outcomes related to reproduction, education and…

Associations of the MCM6-rs3754686 proxy for milk intake in Mediterranean and American populations with cardiovascular biomarkers, disease and mortal…

2016

Controversy persists on the association between dairy products, especially milk, and cardiovascular diseases (CVD). Genetic proxies may improve dairy intake estimations, and clarify diet-disease relationships through Mendelian randomization. We meta-analytically (n T (nonpersistence>persistence), dairy intake, and CVD biomarkers in American (Hispanics, African-American and Whites) and Mediterranean populations. Moreover, we analyzed longitudinal associations with milk, CVD and mortality in PREDIMED), a randomized Mediterranean diet (MedDiet) intervention trial (n = 7185). The MCM6-rs3754686/MCM6-rs309180 (as proxy), LP-allele (T) was strongly associated with higher milk intake, but inconsis…

No Association Between Vitamin D Status and Risk of Barrett's Esophagus or Esophageal Adenocarcinoma: A Mendelian Randomization Study.

2019

Contains fulltext : 215282.pdf (Publisher’s version ) (Closed access) BACKGROUND & AIMS: Epidemiology studies of circulating concentrations of 25 hydroxy vitamin D (25(OH)D) and risk of esophageal adenocarcinoma (EAC) have produced conflicting results. We conducted a Mendelian randomization study to determine the associations between circulating concentrations of 25(OH)D and risks of EAC and its precursor, Barrett's esophagus (BE). METHODS: We conducted a Mendelian randomization study using a 2-sample (summary data) approach. Six single-nucleotide polymorphisms (SNPs; rs3755967, rs10741657, rs12785878, rs10745742, rs8018720, and rs17216707) associated with circulating concentrations of 25(O…

2022

This study quantifies the causal effect of birth weight on cardiovascular biomarkers in adulthood using the Cardiovascular Risk in Young Finns Study (YFS). We apply a multivariable Mendelian randomization (MVMR) method that provides a novel approach to improve inference in causal analysis based on a mediation framework. The results show that birth weight is linked to triglyceride levels (β = -0.294; 95% CI [-0.591, 0.003]) but not to low-density lipoprotein (LDL) cholesterol levels (β = 0.007; 95% CI [-0.168, 0.183]). The total effect of birth weight on triglyceride levels is partly offset by a mediation pathway linking birth weight to adult BMI (β = 0.111; 95% CI [-0.013, 0.234]). The nega…

The association between coffee and caffeine consumption and renal function: insight from individual-level data, Mendelian randomization, and meta-ana…

2022

IntroductionBy applying on two-sample Mendelian randomization and systematic review and meta-analysis we investigated the association between caffeine and coffee intake with prevalent CKD and markers of renal function.Material and methodsFor 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 the largest ever GWAS conducted on coffee intake (N=91,462) and kidney function.ResultsFinally, we included the data of 18,436 participants, 6.9% had prevalent CKD (based on eGFR). Caffeine intake for general population was 131.1±1.1 mg. The percentage of participants with CKD, by caffeine quartile w…

Genome-wide Association Analysis in Humans Links Nucleotide Metabolism to Leukocyte Telomere Length

2020

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…

Sex-Specific Differences in the Control of Serum Concentrations of Glycine in Subjects with Metabolic Syndrome and Mendelian Randomization Analysis f…

2020

OBJECTIVES: Glycine is a novel circulating marker for metabolic diseases associated with lower type-2 diabetes and protection against obesity in some studies. Circulating glycine levels are genetically determined under the control of several loci. The locus most strongly associated is the carbamoyl-phosphate synthase I (CPS1). Interestingly, some sex-specific genome-wide association studies (GWAS) showed differences in the effect of the main single nucleotide polymorphisms (SNPs) in this locus on glycine levels (significant sex * CPS1 interactions). However, the potential mechanisms explaining this sex-heterogeneity are unknown. Therefore, our aims were: 1) to analyze whether the sex * CPS1…