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 (P = 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.
Bibliographical noteFunding Information:
We are grateful to P.M. Visscher for advice, support, and feedback. We thank S. Cunningham and N. Galla for research assistance. This research was carried out under the auspices of the Social Science Genetic Association Consortium (SSGAC). The SSGAC seeks to facilitate studies that investigate the influence of genes on human behavior, well-being, and social-scientific outcomes using large GWAS meta-analyses. The SSGAC also provides opportunities for replication and promotes the collection of accurately measured, harmonized phenotypes across cohorts. The SSGAC operates as a working group within the CHARGE Consortium. This research has also been conducted using the UK Biobank Resource. The study was supported by funding from the US National Science Foundation (EAGER: 'Workshop for the Formation of a Social Science Genetic Association Consortium'), a supplementary grant from the National Institute of Health Office of Behavioral and Social Science Research, the Ragnar Söderberg Foundation (E9/11), the Swedish Research Council (421-2013-1061), the Jan Wallander and Tom Hedelius Foundation, an ERC Consolidator Grant (647648 EdGe), the Pershing Square Fund of the Foundations of Human Behavior, and the NIA/NIH through grants P01-AG005842, P01-AG005842-20S2, P30-AG012810, and T32-AG000186-23 to NBER and R01-AG042568-02 to the University of Southern California. A full list of acknowledgments is provided
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