Person:

Kawachi, Ichiro

Context Anxiety disorders are common, with a lifetime prevalence of 20% in the U.S., and are responsible for substantial burdens of disability, missed work days and health care utilization. To date, no causal genetic variants have been identified for anxiety, anxiety disorders, or related traits. Objective: To investigate whether a phobic anxiety symptom score was associated with 3 alternative polygenic risk scores, derived from external genome-wide association studies of anxiety, an internally estimated agnostic polygenic score, or previously identified candidate genes. Design: Longitudinal follow-up study. Using linear and logistic regression we investigated whether phobic anxiety was associated with polygenic risk scores derived from internal, leave-one out genome-wide association studies, from 31 candidate genes, and from out-of-sample genome-wide association weights previously shown to predict depression and anxiety in another cohort. Setting and Participants: Study participants (n = 11,127) were individuals from the Nurses' Health Study and Health Professionals Follow-up Study. Main Outcome Measure: Anxiety symptoms were assessed via the 8-item phobic anxiety scale of the Crown Crisp Index at two time points, from which a continuous phenotype score was derived. Results: We found no genome-wide significant associations with phobic anxiety. Phobic anxiety was also not associated with a polygenic risk score derived from the genome-wide association study beta weights using liberal p-value thresholds; with a previously published genome-wide polygenic score; or with a candidate gene risk score based on 31 genes previously hypothesized to predict anxiety. Conclusion: There is a substantial gap between twin-study heritability estimates of anxiety disorders ranging between 20–40% and heritability explained by genome-wide association results. New approaches such as improved genome imputations, application of gene expression and biological pathways information, and incorporating social or environmental modifiers of genetic risks may be necessary to identify significant genetic predictors of anxiety.

While research has suggested that being married may confer a health advantage, few studies to date have investigated the role of marital status in the development of type 2 diabetes. We examined whether men who are not married have increased risk of incident type 2 diabetes in the Health Professionals Follow-up Study. Men (n = 41,378) who were free of T2D in 1986, were followed for ≤22 years with biennial reports of T2D, marital status and covariates. Cox proportional hazard models were used to compare risk of incident T2D by marital status (married vs unmarried and married vs never married, divorced/separated, or widowed). There were 2,952 cases of incident T2D. Compared to married men, unmarried men had a 16% higher risk of developing T2D (95%CI:1.04,1.30), adjusting for age, family history of diabetes, ethnicity, lifestyle and body mass index (BMI). Relative risks (RR) for developing T2D differed for divorced/separated (1.09 [95%CI: 0.94,1.27]), widowed (1.29 [95%CI:1.06,1.57]), and never married (1.17 [95%CI:0.91,1.52]) after adjusting for age, family history of diabetes and ethnicity. Adjusting for lifestyle and BMI, the RR for T2D associated with widowhood was no longer significant (RR:1.16 [95%CI:0.95,1.41]). When allowing for a 2-year lag period between marital status and disease, RRs of T2D for widowers were augmented and borderline significant (RR:1.24 [95%CI:1.00,1.54]) after full adjustment. In conclusion, not being married, and more specifically, widowhood was more consistently associated with an increased risk of type 2 diabetes in men and this may be mediated, in part, through unfavorable changes in lifestyle, diet and adiposity.