Abstract
BACKGROUND: Psychiatric disorders are among the largest and fastest-growing categories of the global disease burden. However, limited effort has been made to further elucidate associations between socioeconomic factors and psychiatric disorders from a genetic perspective.
METHODS: We randomly divided 501,882 participants in the UK Biobank cohort with socioeconomic Townsend deprivation index (TDI) data into a discovery cohort and a replication cohort. For both cohorts, we first conducted regression analyses to evaluate the associations between the TDI and common psychiatric disorders or traits, including anxiety, bipolar disorder, self-harm, and depression (based on self-reported depression and Patient Health Questionnaire scores). We then performed a genome-wide gene-by-environment interaction study using PLINK 2.0 with the TDI as an environmental factor to explore interaction effects.
RESULTS: In the discovery cohort, significant associations were observed between the TDI and psychiatric disorders (p < 4.00 × 10-16), including anxiety (odds ratio [OR] = 1.08, 95% confidence interval [CI] = 1.07-1.10), bipolar disorder (OR = 1.42, 95% CI = 1.36-1.48), self-harm (OR = 1.21, 95% CI = 1.19-1.23), self-reported depression (OR = 1.22, 95% CI = 1.20-1.24), and Patient Health Questionnaire scores (β = .07, SE = 0.004). We observed similar significant associations in the replication cohort. In addition, multiple candidate loci were identified by the genome-wide gene-by-environment interaction study, including rs10886438 at 10q26.11 (GRK5) (p = 5.72 × 10-11) for Patient Health Questionnaire scores and rs162553 at 2p22.2 (CYP1B1) (p = 2.25 × 10-9) for self-harm.
CONCLUSIONS: Our findings suggest the relevance of the TDI to psychiatric disorders. The genome-wide gene-by-environment interaction study identified several candidate genes interacting with the TDI, providing novel clues for understanding the biological mechanism of associations between the TDI and psychiatric disorders.