|Title||GENOME-WIDE ASSOCIATION STUDY (GWAS) AND GENOME-WIDE BY ENVIRONMENT INTERACTION STUDY (GWEIS) OF DEPRESSIVE SYMPTOMS IN AFRICAN AMERICAN AND HISPANIC/LATINA WOMEN.|
|Publication Type||Journal Article|
|Year of Publication||2016|
|Authors||Dunn, EC, Wiste, A, Radmanesh, F, Almli, LM, Gogarten, SM, Sofer, T, Faul, J, 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, SM, Ressler, KJ, Rosand, J, Wassertheil-Smoller, S, Smoller, JW|
|Date Published||2016 Apr|
|Keywords||African 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|
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.
|User Guide Notes|
|Alternate Journal||Depress Anxiety|
|PubMed Central ID||PMC4826276|
|Grant List||RC4 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