1,431 research outputs found
Erratum to “Short communication:Genetic association between schizophrenia and cannabis use” [Drug and Alcohol Dependence 171 (2017) 117–121](S0376871616309292)(10.1016/j.drugalcdep.2016.09.022)
No full textThe publisher regrets that in the online version of this article, authors Nathan A. Gillespie, Gonneke Willemsen, Jouke-Jan Hottenga, Dorret I. Boomsma and Jacqueline M. Vink were omitted from the author list. The correct list of authors is shown below: Karin J.H. Verweij∗, Abdel Abdellaoui, Michel G. Nivard, Alberto Sainz Cort, LannieLigthart, Harmen H.M. Draisma, Camelia C. Minică, International Cannabis Consortium1, Nathan A. Gillespie, Gonneke Willemsen, Jouke-Jan Hottenga, Dorret I. Boomsma, Jacqueline M. Vink. The publisher would like to apologise for any inconvenience caused.</p
Polygenic scores associated with educational attainment in adults predict educational achievement and ADHD symptoms in children
No full textThe following people who are not listed as co-authors on this manuscript contributed to the original GWAS meta-analysis on educational attainment [Rietveld et al., 2013], on which the present paper is based. Data access has been granted under section 4 of the Data Sharing Agreement of the Social Science Genetic Association Consortium (SSGAC). The views presented in the present paper may not reflect the opinions of the individuals listed below. The SSGAC is grateful to the authors of [Rietveld et al., 2013] for providing the meta-analysis data. We thank: Abdel Abdellaoui ... Debbie A. Lawlor ... et al.Abstract not availableEveline L. de Zeeuw, Catharina E.M. van Beijsterveldt, Tina J. Glasner, M. Bartels, Erik A. Ehli, Gareth E. Davies, James J. Hudziak, Social Science Genetic Association Consortium, Cornelius A. Rietveld, Maria M. Groen-Blokhuis, Jouke Jan Hottenga, Eco J.C. de Geus, and Dorret I. Boomsm
Supplement: Unidirectional and Bidirectional Causation between Smoking and Blood DNA Methylation: Evidence from Twin-based Mendelian Randomisation
No full textThis project contains the supplementary materials of the manuscript:
Singh M., Dolan C.V., Lapato D.M., Hottenga J.-J., Pool R., Verhulst B., Boomsma D.I., Breeze C.E., de Geus E.J.C., Hemani G., Min J.L., Peterson R.E., Maes H.H.M., van Dongen J. & Neale M.C. (2025). Unidirectional and Bidirectional Causation between Smoking and Blood DNA Methylation: Evidence from Twin-based Mendelian Randomisation. European Journal of Epidemiology. https://doi.org/10.1007/s10654-024-01187-
Hundreds of variants clustered in genomic loci and biological pathways affect human height
No full textMost common human traits and diseases have a polygenic pattern of inheritance: DNA sequence variants at many genetic loci influence the phenotype. Genome-wide association (GWA) studies have identified more than 600 variants associated with human traits(1), but these typically explain small fractions of phenotypic variation, raising questions about the use of further studies. Here, using 183,727 individuals, we show that hundreds of genetic variants, in at least 180 loci, influence adult height, a highly heritable and classic polygenic trait(2,3). The large number of loci reveals patterns with important implications for genetic studies of common human diseases and traits. First, the 180 loci are not random, but instead are enriched for genes that are connected in biological pathways (P = 0.016) and that underlie skeletal growth defects (P<0.001). Second, the likely causal gene is often located near the most strongly associated variant: in 13 of 21 loci containing a known skeletal growth gene, that gene was closest to the associated variant. Third, at least 19 loci have multiple independently associated variants, suggesting that allelic heterogeneity is a frequent feature of polygenic traits, that comprehensive explorations of already-discovered loci should discover additional variants and that an appreciable fraction of associated loci may have been identified. Fourth, associated variants are enriched for likely functional effects on genes, being over-represented among variants that alter amino-acid structure of proteins and expression levels of nearby genes. Our data explain approximately 10% of the phenotypic variation in height, and we estimate that unidentified common variants of similar effect sizes would increase this figure to approximately 16% of phenotypic variation (approximately 20% of heritable variation). Although additional approaches are needed to dissect the genetic architecture of polygenic human traits fully, our findings indicate that GWA studies can identify large numbers of loci that implicate biologically relevant genes and pathways
Genome-Wide Association Study of Food Liking in 162,000 People Uncovers the Genetic Bases of Food Liking
No full textAssociation analyses of 249,796 individuals reveal 18 new loci associated with body mass index
No full textObesity is globally prevalent and highly heritable, but its underlying genetic factors remain largely elusive. To identify genetic loci for obesity susceptibility, we examined associations between body mass index and similar to 2.8 million SNPs in up to 123,865 individuals with targeted follow up of 42 SNPs in up to 125,931 additional individuals. We confirmed 14 known obesity susceptibility loci and identified 18 new loci associated with body mass index (P < 5 x 10(-8)), one of which includes a copy number variant near GPRC5B. Some loci (at MC4R, POMC, SH2B1 and BDNF) map near key hypothalamic regulators of energy balance, and one of these loci is near GIPR, an incretin receptor. Furthermore, genes in other newly associated loci may provide new insights into human body weight regulation
Genome-wide meta-analysis identifies 11 new loci for anthropometric traits and provides insights into genetic architecture
No full textApproaches exploiting trait distribution extremes may be used to identify loci associated with common traits, but it is unknown whether these loci are generalizable to the broader population. In a genome-wide search for loci associated with the upper versus the lower 5th percentiles of body mass index, height and waist-to-hip ratio, as well as clinical classes of obesity, including up to 263,407 individuals of European ancestry, we identified 4 new loci (IGFBP4, H6PD, RSRC1 and PPP2R2A) influencing height detected in the distribution tails and 7 new loci (HNF4G, RPTOR, GNAT2, MRPS33P4, ADCY9, HS6ST3 and ZZZ3) for clinical classes of obesity. Further, we find a large overlap in genetic structure and the distribution of variants between traits based on extremes and the general population and little etiological heterogeneity between obesity subgroups
Meta-analyses identify 13 loci associated with age at menopause and highlight DNA repair and immune pathways
No full textTo newly identify loci for age at natural menopause, we carried out a meta-analysis of 22 genome-wide association studies (GWAS) in 38,968 women of European descent, with replication in up to 14,435 women. In addition to four known loci, we identified 13 loci newly associated with age at natural menopause (at P < 5 × 10(-8)). Candidate genes located at these newly associated loci include genes implicated in DNA repair (EXO1, HELQ, UIMC1, FAM175A, FANCI, TLK1, POLG and PRIM1) and immune function (IL11, NLRP11 and PRRC2A (also known as BAT2)). Gene-set enrichment pathway analyses using the full GWAS data set identified exoDNase, NF-κB signaling and mitochondrial dysfunction as biological processes related to timing of menopause
Identification of heart rate-associated loci and their effects on cardiac conduction and rhythm disorders
No full textElevated resting heart rate is associated with greater risk of cardiovascular disease and mortality. In a 2-stage meta-analysis of genome-wide association studies in up to 181,171 individuals, we identified 14 new loci associated with heart rate and confirmed associations with all 7 previously established loci. Experimental downregulation of gene expression in Drosophila melanogaster and Danio rerio identified 20 genes at 11 loci that are relevant for heart rate regulation and highlight a role for genes involved in signal transmission, embryonic cardiac development and the pathophysiology of dilated cardiomyopathy, congenital heart failure and/or sudden cardiac death. In addition, genetic susceptibility to increased heart rate is associated with altered cardiac conduction and reduced risk of sick sinus syndrome, and both heart rate-increasing and heart rate-decreasing variants associate with risk of atrial fibrillation. Our findings provide fresh insights into the mechanisms regulating heart rate and identify new therapeutic targets
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