TY - JOUR T1 - GENOME-WIDE ASSOCIATION STUDY (GWAS) AND GENOME-WIDE BY ENVIRONMENT INTERACTION STUDY (GWEIS) OF DEPRESSIVE SYMPTOMS IN AFRICAN AMERICAN AND HISPANIC/LATINA WOMEN. JF - Depress Anxiety Y1 - 2016 A1 - Dunn, Erin C A1 - Wiste, Anna A1 - Radmanesh, Farid A1 - Almli, Lynn M A1 - Gogarten, Stephanie M A1 - Sofer, Tamar A1 - Jessica Faul A1 - Sharon L R Kardia A1 - Jennifer A Smith A1 - David R Weir A1 - Wei Zhao A1 - Soare, Thomas W A1 - Saira S Mirza A1 - Karin Hek A1 - Henning Tiemeier A1 - Goveas, Joseph S A1 - Sarto, Gloria E A1 - Snively, Beverly M A1 - Marilyn C Cornelis A1 - Karestan C Koenen A1 - Kraft, Peter A1 - Shaun M Purcell A1 - Ressler, Kerry J A1 - Rosand, Jonathan A1 - Wassertheil-Smoller, Sylvia A1 - Smoller, Jordan W KW - African Americans KW - Aged KW - depression KW - Female KW - Gene-Environment Interaction KW - Genome-Wide Association Study KW - Hispanic Americans KW - Humans KW - Life Change Events KW - Middle Aged KW - Phenotype KW - Polymorphism, Single Nucleotide KW - Risk Factors KW - Self Report AB -

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.

VL - 33 IS - 4 U1 - http://www.ncbi.nlm.nih.gov/pubmed/27038408?dopt=Abstract ER -