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.

Objective To evaluate rheumatoid arthritis (RA) and mortality risk among women followed prospectively in the Nurses’ Health Study (NHS). Methods We analyzed 119,209 women in the NHS who reported no connective tissue disease at enrollment in 1976. Comorbidity and lifestyle data were collected through biennial questionnaires. Incident RA cases were validated by medical records review. Cause of death was determined by death certificate and medical records review. Cox regression models estimated hazard ratios (HRs) and 95% confidence intervals (95% CIs) for all-cause, cardiovascular disease (CVD), cancer, and respiratory disease mortality for women with RA compared to those without RA. Results We validated 964 incident RA cases and identified 28,808 deaths during 36 years of prospective follow-up. Of 307 deaths among women with RA, 80 (26%) were from cancer, 70 (23%) were from CVD, and 44 (14%) were from respiratory causes. Women with RA had increased total mortality (HR 1.40, 95% CI 1.25–1.57) compared to those without RA, independent of mortality risk factors, including smoking. RA was associated with significantly increased respiratory disease mortality (HR 2.06, 95% CI 1.51–2.80) and cardiovascular disease mortality (HR 1.45, 95% CI 1.14–1.83), but not cancer mortality (HR 0.93, 95% CI 0.74–1.15). For women with seropositive RA, respiratory disease mortality was nearly 3-fold higher than among non-RA women (HR 2.67, 95% CI 1.89–3.77). Conclusion Women with RA had significantly increased mortality compared to those without RA. Respiratory disease and cardiovascular disease mortality were both significantly elevated for women with RA. The nearly 3-fold increased relative risk of respiratory disease mortality was observed only for those with seropositive RA.

Objective Previous studies on the association between religious service attendance and depression have been mostly cross-sectional, subject to reverse causation, and did not account for the potential feedback between religious service attendance and depression. We prospectively evaluated whether religious service attendance decreased risk of subsequent risk of depression and whether depression increased subsequent cessation of service attendance, while explicitly accounting for feedback with potential effects in both directions. Method We included a total of 48,984 U.S. nurses who were participants of the Nurses’ Health Study with mean age 58 years and who were followed up from 1996 to 2008. Religious services attendance was self-reported in 1992, 1996, 2000, and 2004. Depression was defined as self-reported physician-diagnosed clinical depression, regular anti-depressant use, or severe depressive symptoms. Multivariate logistic regression and marginal structural models were used to estimate the odds ratio of developing incident depression, adjusted for baseline religious service attendance, baseline depression and time-varying covariates. Results Compared with women who never attended services, women who had most frequent and recent religious service attendance had the lowest risk of developing depression (odds ratio [OR] =0.71, 95% confidence interval [CI]:0.62–0.82). Compared with women who were not depressed, women with depression were less likely to subsequently attend religious services once or more per week (OR=0.74, 95% CI: 0.68–0.80). Conclusions In this study of U.S. women, there is evidence that higher frequency of religious service attendance decreased the risk of incident depression and women with depression were less likely to subsequently attend services.