@article{a6cfb9a4e5854ea4b9e30e251c8f0456,
title = "Genome-wide association study (GWAS) and genome-wide by environment interaction study (GWEIS) of depressive symptoms in African American and Hispanic/Latina Women",
abstract = "Background: Genome-wide association studies (GWAS) have made little progress in identifying variants linked to depression. We hypothesized that examining depressive symptoms and considering gene-environment interaction (GxE) might improve efficiency for gene discovery. We therefore conducted a GWAS and genome-wide by environment interaction study (GWEIS) of depressive symptoms. Methods: Using data from the SHARe cohort of the Women{\textquoteright}s Health Initiative, comprising African Americans (n = 7,179) and Hispanics/Latinas (n = 3,138), we examined genetic main effects and GxE with stressful life events and social support. We also conducted a heritability analysis using genome-wide complex trait analysis (GCTA). Replication was attempted in four independent cohorts. Results: No SNPs achieved genome-wide significance for main effects in either discovery sample. The top signals in African Americans were rs73531535 (located 20 kb from GPR139, P = 5.75 × 10−8) and rs75407252 (intronic to CACNA2D3, P = 6.99 × 10−7). In Hispanics/Latinas, the top signals were rs2532087 (located 27 kb from CD38, P = 2.44 × 10−7) and rs4542757 (intronic to DCC, P = 7.31 × 10−7). In the GEWIS with stressful life events, one interaction signal was genome-wide significant in African Americans (rs4652467; P = 4.10 × 10−10; located 14 kb from CEP350). This interaction was not observed in a smaller replication cohort. Although heritability estimates for depressive symptoms and stressful life events were each less than 10%, they were strongly genetically correlated (rG = 0.95), suggesting that common variation underlying self-reported depressive symptoms and stressful life event exposure, though modest on their own, were highly overlapping in this sample. Conclusions: Our results underscore the need for larger samples, more GEWIS, and greater investigation into genetic and environmental determinants of depressive symptoms in minorities.",
keywords = "Depression, Gene-environment interaction, Genome-wide association study, Social support, Stressful life events",
author = "Dunn, {Erin C.} and Anna Wiste and Farid Radmanesh and Almli, {Lynn M.} and Gogarten, {Stephanie M.} and Tamar Sofer and Faul, {Jessica D.} and Kardia, {Sharon L.R.} and Smith, {Jennifer A.} and Weir, {David R.} and Wei Zhao and Soare, {Thomas W.} and Mirza, {Saira S.} and Karin Hek and Henning Tiemeier and Goveas, {Joseph S.} and Sarto, {Gloria E.} and Snively, {Beverly M.} and Marilyn Cornelis and Koenen, {Karestan C.} and Peter Kraft and Shaun Purcell and Ressler, {Kerry J.} and Jonathan Rosand and Sylvia Wassertheil-Smoller and Smoller, {Jordan W.}",
note = "Funding Information: Contract grant sponsor: National Institute of Mental Health of the National Institutes of Health; Contract grant numbers: K01MH102403 and K24MH094614; Contract grant sponsor: NARSAD Young Investigator Grant from the Brain & Behavior Research Foundation. Contract grant sponsor: the National Heart, Lung, and Blood Institute; Contract grant sponsor: U.S. Department of Health and Human Services; Contract grant numbers: HHSN268201100046C, HHSN268201100001C, HHSN 268201100002C, HHSN268201100003C, HHSN268201100004C, and HHSN271201100004C. Contract grant sponsor: National Institute on Aging; Contract grant number: NIA U01AG009740, RC2 AG036495, and RC4 AG039029. Funding Information: Research reported in this publication was supported by the National Institute of Mental Health of the National Institutes of Health under Award Number K01MH102403 (E.C.D.) and K24MH094614 (Dr. S.W.-S.) and by a NARSAD Young Investigator Grant from the Brain & Behavior Research Foundation (E.C.D.). The WHI program is funded by the National Heart, Lung, and Blood Institute, National Institutes of Health, U.S. Department of Health and Human Services through contracts HHSN268201100046C, HHSN 268201100001C, HHSN268201100002C, HHSN 268201100003C, HHSN268201100004C, and HHSN 271201100004C. HRS is supported by the National Institute on Aging (NIA U01AG009740). The genotyp-ing was funded separately by the National Institute on Aging (RC2 AG036495, RC4 AG039029). Genotyping was conducted by the NIH Center for Inherited Disease Research (CIDR) at Johns Hopkins University. Geno-typing quality control and final preparation of the data were performed by the Genetics Coordinating Center at the University of Washington. Publisher Copyright: {\textcopyright} 2016 Wiley Periodicals, Inc.",
year = "2016",
month = apr,
day = "1",
doi = "10.1002/da.22484",
language = "English (US)",
volume = "33",
pages = "265--280",
journal = "Anxiety",
issn = "1091-4269",
publisher = "Wiley-Blackwell",
number = "4",
}
