0000000000153358
AUTHOR
Ville Karhunen
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…
Additional file 2: of DNA methylation links prenatal smoking exposure to later life health outcomes in offspring
Characteristics of the participants based on exposure to maternal smoking during pregnancy in the ALSPAC studies. (DOCX 13 kb)
Additional file 6: of DNA methylation links prenatal smoking exposure to later life health outcomes in offspring
CpG sites and their association with methylation in the ARIES cord blood data. (DOCX 14 kb)
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…
Additional file 4: of DNA methylation links prenatal smoking exposure to later life health outcomes in offspring
Paternal smoking-adjusted association results of exposure to maternal smoking during pregnancy and offspring peripheral blood DNA methylation for the top CpG sites. (DOCX 14 kb)
Additional file 7: of DNA methylation links prenatal smoking exposure to later life health outcomes in offspring
Effect sizes and their 95% confidence intervals of each available SNP-CpG association across different time points in the ARIES data. (DOCX 108 kb)
Additional file 6: of DNA methylation links prenatal smoking exposure to later life health outcomes in offspring
CpG sites and their association with methylation in the ARIES cord blood data. (DOCX 14 kb)
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…
Additional file 4: of DNA methylation links prenatal smoking exposure to later life health outcomes in offspring
Paternal smoking-adjusted association results of exposure to maternal smoking during pregnancy and offspring peripheral blood DNA methylation for the top CpG sites. (DOCX 14 kb)
Additional file 5: of DNA methylation links prenatal smoking exposure to later life health outcomes in offspring
Mediation analysis examining the mediated effect of maternal smoking during pregnancy on schizophrenia-related personality traits and inflammatory bowel syndrome in the NFBC 1966 cohort. (DOCX 15 kb)
Additional file 3: of DNA methylation links prenatal smoking exposure to later life health outcomes in offspring
Characteristics of the participants based on exposure to maternal smoking during pregnancy in the IOWBC. (DOCX 12 kb)
Additional file 1: of DNA methylation links prenatal smoking exposure to later life health outcomes in offspring
Characteristics of the participants based on exposure to maternal smoking during pregnancy in the NFBC cohorts. (DOCX 14 kb)
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…
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…
DNA methylation links prenatal smoking exposure to later life health outcomes in offspring
Background Maternal smoking during pregnancy is associated with adverse offspring health outcomes across their life course. We hypothesize that DNA methylation is a potential mediator of this relationship. Methods We examined the association of prenatal maternal smoking with offspring blood DNA methylation in 2821 individuals (age 16 to 48 years) from five prospective birth cohort studies and perform Mendelian randomization and mediation analyses to assess whether methylation markers have causal effects on disease outcomes in the offspring. Results We identify 69 differentially methylated CpGs in 36 genomic regions (P value < 1 × 10−7) associated with exposure to maternal smoking in adolesc…
Genome-wide association analyses of risk tolerance and risky behaviors in over 1 million individuals identify hundreds of loci and shared genetic influences1
AbstractHumans vary substantially in their willingness to take risks. In a combined sample of over one million individuals, we conducted genome-wide association studies (GWAS) of general risk tolerance, adventurousness, and risky behaviors in the driving, drinking, smoking, and sexual domains. We identified 611 approximately independent genetic loci associated with at least one of our phenotypes, including 124 with general risk tolerance. We report evidence of substantial shared genetic influences across general risk tolerance and risky behaviors: 72 of the 124 general risk tolerance loci contain a lead SNP for at least one of our other GWAS, and general risk tolerance is moderately to stro…