Genetic variants associated with subjective well-being, depressive symptoms, and neuroticism identified through genome-wide analyses

Abstract

We conducted genome-wide association studies of three phenotypes: subjective well-being (N = 298,420), depressive symptoms (N = 161,460), and neuroticism (N = 170,910). We identified three variants associated with subjective well-being, two with depressive symptoms, and eleven with neuroticism, including two inversion polymorphisms. The two depressive symptoms loci replicate in an independent depression sample. Joint analyses that exploit the high genetic correlations between the phenotypes (|ρ̂| ≈ 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/pancreas tissues are strongly enriched for association.

Genetic effects on gene expression across human tissues

“…By integrating GTEx data with summary statistics from diverse GWAS, we observed that half of complex trait- associated loci co-localize with a GTEx eQTL. GTEx data have already served as a valuable community resource for the identification of the tissue-specific regulatory effects underlying variants associated with human disease phenotypes 58–61 .…”

Genome-Wide Association Study of Loneliness Demonstrates a Role for Common Variation

“…We have previously reported that genetic variation in the initial sensitivity to the euphoric effects of amphetamine is genetically correlated with the risk for both schizophrenia and ADHD (Hart et al, 2014). That provocative finding Table 4 Associations between Polygenic Scores for Neuroticism from SSGAC (Okbay et al, 2016) The testing set was an independent set using the data of HRS; the polygenic scores have been standardized, and hence the β coefficients from the Neuroticism linear regression model correspond to a 1 SD change in the polygenic score. provides an example of using genetic variation in a nondisease trait to obtain novel insights into the genetic basis of psychiatric diseases.…”

Selection against variants in the genome associated with educational attainment

“…It is known to tag the H2 haplotype of a common inversion on chromosome 17 that was shown to exhibit characteristics consistent with having been positive-selected (23). It has subsequently been shown that H2 is also associated with reduced intracranial volume (24,25) and neuroticism (26). Combining our male and female data, the minor allele of rs192818565 is significantly associated with more children (P = 5.2 × 10 ) and having children earlier (P = 2.2 × 10…”