%0 Journal Article
%T Genome-wide association study (GWAS) and genome-wide by environment interaction study (GWEIS) of depressive symptoms in African American and Hispanic/Latina women
%J Depression and anxiety
%D 2016
%A Dunn, Erin C.
%A Wiste, Anna
%A Radmanesh, Farid
%A Almli, Lynn M.
%A Gogarten, Stephanie M.
%A Sofer, Tamar
%A Faul, Jessica D.
%A Kardia, Sharon L. R.
%A Smith, Jennifer A.
%A Weir, David R.
%A Zhao, Wei
%A Soare, Thomas W.
%A Mirza, Saira S.
%A Hek, Karin
%A Tiemeier, Henning
%A Goveas, Joseph S.
%A Sarto, Gloria E.
%A Snively, Beverly M.
%A Cornelis, Marilyn C.
%A Koenen, Karestan C.
%A Kraft, Peter
%A Purcell, Shaun
%A Ressler, Kerry J.
%A Rosand, Jonathan
%A Wassertheil-Smoller, Sylvia
%A Smoller, Jordan W.
%V 33
%N 4
%P 265-280
%X 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.
© 2016 Wiley Periodicals, Inc. Language: en
%G en
%I John Wiley and Sons
%@ 1091-4269
%U http://dx.doi.org/10.1002/da.22484