Very few genetic variants have been associated with depression and neuroticism, likely because of limitations on sample size in previous studies. Subjective well-being, a phenotype that is genetically correlated with both of these traits, has not yet been studied with genome-wide data. We conducted genome-wide association studies of three phenotypes: subjective well-being (n = 298,420), depressive symptoms (n = 161,460), and neuroticism (n = 170,911). We identify 3 variants associated with subjective well-being, 2 variants associated with depressive symptoms, and 11 variants associated with neuroticism, including 2 inversion polymorphisms. The two loci associated with depressive symptoms replicate in an independent depression sample. Joint analyses that exploit the high genetic correlations between the phenotypes (|? | 0.8) strengthen the overall credibility of the findings and allow us to identify additional variants. Across our phenotypes, loci regulating expression in central nervous system and adrenal or pancreas tissues are strongly enriched for association.
Aysu Okbay, Bart M L Baselmans, Jan-Emmanuel De Neve, Patrick Turley, Michel G Nivard, Mark Alan Fontana, S Fleur W Meddens, Richard Karlsson Linn r & Cornelius A Rietveld, et al. Genetic variants associated with subjective well-being, depressive symptoms, and neuroticism identified through genome-wide analyses. Nature genetics 2016 48;6: 624 - 633 doi:10.1038/ng.3552
The Social Science Genetic Association Consortium
We, the Social Science Genetic Association Consortium (SSGAC), aim to bring together the expertise of medical geneticists and social scientists to study how a range of health-relevant outcomes are influenced by specific genetic variants, the environment (including lifestyle), and their interaction. In accessing the U.K. Biobank data, we are specifically interested in the following health-relevant outcomes: cognitive function, dementia, depression, smoking, and alcohol drinking. Our research will contribute to quantifying how several risk factors (e.g. lifestyle, environment, genes), both separately and in combination, influence public health and well-being. Incorporating insights from the social sciences and investigating social scientific outcomes helps to achieve this objective. For example, a GWAS on subjective well-being in a very large sample could identify genetic factors associated with (absence of) depression that would not be possible to identify by studying depression directly in a much smaller sample. Furthermore, accurate polygenic risk scores can be used to study how lifestyle and environmental factors mediate genetic effects on health. We will use several methods, e.g.:
? Genomewide association studies (GWAS) that aim to identify individual genetic variants associated with a particular outcome.
? GWAS of a ?proxy phenotype??a biologically-distal phenotype available in larger samples?to identify candidate genetic variants for association with a health-relevant outcome available in smaller samples.
? Estimation of economic and statistical models of health-relevant outcomes as a function of genetic variants, environmental factors, and their interaction. We will typically use all available observations in the UKB that (i) are of European decent, (ii) have been successfully genotyped, and (iii) have measures of the phenotype(s) under investigation.
|Lead investigator:||Professor Daniel Benjamin|
|Lead institution:||National Bureau of Economic Research|
6 related Returns
|Return ID||App ID||Description||Archive Date|
|3065||11425||Are Bigger Brains Smarter? Evidence From a Large-Scale Preregistered Study||14 Dec 2020|
|717||11425||Gemome-wide association study identifies 74 loci associated with educational attainment||17 Oct 2017|
|2159||11425||Genome-wide association analyses of risk tolerance and risky behaviors in over 1 million individuals identify hundreds of loci and shared genetic influences||7 Apr 2020|
|2887||11425||Multi-trait analysis of genome-wide association summary statistics using MTAG||27 Nov 2020|
|1782||11425||Pleiotropy-robust Mendelian Randomization||30 Sep 2019|
|3586||11425||Resource Profile and User Guide of the Polygenic Index Repository||24 Jun 2021|
|719||Genetic variants associated with subjective well-being, depressive symptoms, and neuroticism identified through genome-wide analyses||Okbay A et al.||2016||Nat Genet|