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

Manhattan plots of GWAS results(a) Subjective well-being (N = 298,420), (b) Depressive symptoms (N = 180,866), (c) Neuroticism (N = 170,911). The x-axis is chromosomal position, and the y-axis is the significance on a −log10 scale. The upper dashed line marks the threshold for genome-wide significance (p = 5×10 8); the lower line marks the threshold for nominal significance (p = 10 5). Each approximately independent genome-wide significant association (“lead SNP”) is marked by ×. Each lead SNP is the lowest p-value SNP within the locus, as defined by our clumping algorithm (Supplementary Note).

Genetic correlations with bars representing 95% confidence intervalsThe correlations are estimated using bivariate LD Score (LDSC) regression. (a) Genetic correlations between subjective well-being, depressive symptoms, and neuroticism (“our three phenotypes”), as well as between our three phenotypes and height. (b) Genetic correlations between our three phenotypes and selected neuropsychiatric phenotypes. (c) Genetic correlations between our three phenotypes and selected physical health phenotypes. In (b) and (c), we report the negative of the estimated correlation with depressive symptoms and neuroticism (but not subjective well-being).

Quasi-replication and lookup of lead SNPsIn quasi-replication analyses, we examined whether (a) lead SNPs identified in the subjective well-being meta-analyses are associated with depressive symptoms or neuroticism, (b) lead SNPs identified in the analyses of depressive symptoms are associated with subjective well-being, and (c) lead SNPs identified in the analyses of neuroticism are associated with subjective well-being. The quasi-replication sample is always restricted to non-overlapping cohorts. In a separate lookup exercise, we examined whether lead SNPs for depressive symptoms and neuroticism are associated with depression in an independent sample of 23andMe customers (N = 368,890). The results from this lookup are depicted as green crosses in (b) and (c). Bars represent 95% CIs (not adjusted for multiple testing). For interpretational ease, we choose the reference allele so that positive coefficients imply that the estimated effect is in the predicted direction. Listed below each lead SNP is the nearest gene.

Results from selected biological analyses(a) Estimates of the expected increase in the phenotypic variance accounted for by a SNP due to the SNP’s being in a given category (τc), divided by the LD Score heritability of the phenotype (h2). Each estimate of τc comes from a separate stratified LD Score regression, controlling for the 52 functional annotation categories in the “baseline model.” The bars represent 95% CIs (not adjusted for multiple testing). To benchmark the estimates, we compare them to those obtained from a recent study of height27. (b) Inversion polymorphism on chromosome 8 and the 7 genes for which the inversion is a significant cis-eQTL at FDR < 0.05. The upper half of the figure shows the Manhattan plot for neuroticism for the inversion and surrounding regions. The bottom half shows the squared correlation between the SNPs and the principal component that captures the inversion. The inlay plots the relationship, for each SNP in the inversion region, between the SNP’s significance and its squared correlation with the principal component that captures the inversion.