Jing Ye1, Yan Wen1, Xifang Sun2, Xiaomeng Chu1, Ping Li1, Bolun Cheng1, Shiqiang Cheng1, Li Liu1, Lu Zhang1, Mei Ma1, Xin Qi1, Chujun Liang1, Om Prakash Kafle1, Yumeng Jia1, Cuiyan Wu1, Sen Wang1, Xi Wang1, Yujie Ning1, Shiquan Sun1, Feng Zhang3. 1. Key Laboratory of Trace Elements and Endemic Diseases of National Health and Family Planning Commission, School of Public Health, Health Science Center, Xi'an Jiaotong University, Xi'an, China. 2. Key Laboratory of Trace Elements and Endemic Diseases of National Health and Family Planning Commission, School of Public Health, Health Science Center, Xi'an Jiaotong University, Xi'an, China; Department of Mathematics, School of Science, Xi'an Shiyou University, Xi'an, China. 3. Key Laboratory of Trace Elements and Endemic Diseases of National Health and Family Planning Commission, School of Public Health, Health Science Center, Xi'an Jiaotong University, Xi'an, China. Electronic address: fzhxjtu@mail.xjtu.edu.cn.
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.
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.
Authors: Kate A Duchowny; Sarah F Ackley; Willa D Brenowitz; Jingxuan Wang; Scott C Zimmerman; Michelle R Caunca; M Maria Glymour Journal: JAMA Netw Open Date: 2022-06-01