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

%B Depress Anxiety %V 33 %P 265-80 %8 2016 Apr %G eng %N 4 %1 http://www.ncbi.nlm.nih.gov/pubmed/27038408?dopt=Abstract %R 10.1002/da.22484