GENOME-WIDE ASSOCIATION STUDY (GWAS) AND GENOME-WIDE BY ENVIRONMENT INTERACTION STUDY (GWEIS) OF DEPRESSIVE SYMPTOMS IN AFRICAN AMERICAN AND HISPANIC/LATINA WOMEN.

TitleGENOME-WIDE ASSOCIATION STUDY (GWAS) AND GENOME-WIDE BY ENVIRONMENT INTERACTION STUDY (GWEIS) OF DEPRESSIVE SYMPTOMS IN AFRICAN AMERICAN AND HISPANIC/LATINA WOMEN.
Publication TypeJournal Article
Year of Publication2016
AuthorsDunn, EC, Wiste, A, Radmanesh, F, Almli, LM, Gogarten, SM, Sofer, T, Faul, JD, Kardia, SLR, Smith, JA, Weir, DR, Zhao, W, Soare, TW, Mirza, SS, Hek, K, Tiemeier, H, Goveas, JS, Sarto, GE, Snively, BM, Cornelis, MC, Koenen, KC, Kraft, P, Purcell, S, Ressler, KJ, Rosand, J, Wassertheil-Smoller, S, Smoller, JW
JournalDepress Anxiety
Volume33
Issue4
Pagination265-80
Date Published2016 Apr
ISSN Number1520-6394
KeywordsAfrican Americans, Aged, depression, Female, Gene-Environment Interaction, Genome-Wide Association Study, Hispanic Americans, Humans, Life Change Events, Middle Aged, Phenotype, Polymorphism, Single Nucleotide, Risk Factors, Self Report
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'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.

DOI10.1002/da.22484
User Guide Notes

http://www.ncbi.nlm.nih.gov/pubmed/27038408?dopt=Abstract

Alternate JournalDepress Anxiety
Citation Key8607
PubMed ID27038408
PubMed Central IDPMC4826276
Grant ListRC4 AG039029 / AG / NIA NIH HHS / United States
HHSN268201100001I / HL / NHLBI NIH HHS / United States
K24 MH094614 / MH / NIMH NIH HHS / United States
U01 AG009740 / AG / NIA NIH HHS / United States
L40 MH098379 / MH / NIMH NIH HHS / United States
HHSN268201100004I / HL / NHLBI NIH HHS / United States
HHSN268201100046C / HL / NHLBI NIH HHS / United States
K24MH094614 / MH / NIMH NIH HHS / United States
HHSN268201100003C / WH / WHI NIH HHS / United States
K01 MH102403 / MH / NIMH NIH HHS / United States
HHSN271201100004C / AG / NIA NIH HHS / United States
HHSN268201100002C / WH / WHI NIH HHS / United States
P30 DK020541 / DK / NIDDK NIH HHS / United States
U01AG009740 / AG / NIA NIH HHS / United States
RC2 AG036495 / AG / NIA NIH HHS / United States
HHSN268201100002I / HL / NHLBI NIH HHS / United States
K01MH102403 / MH / NIMH NIH HHS / United States
HHSN268201100001C / WH / WHI NIH HHS / United States
HHSN268201100004C / WH / WHI NIH HHS / United States