To test the lead SNPs for replication, we use the Health and Retirement Study (HRS) and the National Longitudinal Study of Adolescent to Adult Health (Add Health), which both contain high-quality measures of DEP, NEUR, and SWB. Because HRS was included in the SSGAC discovery sample for SWB, we re-ran the GWAS and MTAG analyses for SWB after omitting it. Although our replication samples are too small for well-powered replication analyses of single-SNP associations, we are well powered to test the SNPs jointly. For the set of MTAG-identified lead SNPs for each trait, we regressed the effect sizes in HRS and in Add Health on the MTAG effect sizes, after correcting the MTAG effect-size estimates for the winner’s curse (Supplementary Note). The regression slope for each replication cohort was then meta-analyzed. If the SNP effect sizes taken altogether replicate, then we expect a slope of one. The regression slopes are 0.88 (s.e. = 0.22) for DEP, 0.76 (s.e. = 0.21) for NEUR, and 0.99 (s.e. = 0.33) for SWB (Figure 5). In all cases, the slope is statistically significantly greater than zero (one-sided P=2.16×10−5, 1.87×10−4, and 1.52×10−3, respectively) but not statistically distinguishable from one.
