Depressive symptoms were measured by a 10-item CES-D, social support was measured through the 12-item version of the Interpersonal Support Evaluation List58, and stressful life events measured through a composite measure designed to match the discovery sample. We also assessed top GWAS findings for both Hispanics and African Americans in the Cohorts for Heart and Aging Research in Genomic Epidemiology, which performed the largest meta-analysis GWAS of depressive symptoms to date using 17 European-ancestry population-based studies of older adults where depressive symptoms were measured through the CES-D6. Secondary Analyses We performed five secondary analyses. First, we conducted two sets of meta analyses to determine the degree to which the top GWAS SNPs obtained in African Americans also showed evidence of nominal association in Hispanics/Latinas and vice versa. Second, we reran the GWAS in each sample after additionally adjusting for both SB 1317 price environmental exposures, as both stressful life events and social support were found to make large and unique contributions to the variance in depressive symptoms. Third, we performed an analysis using genome-wide complex trait analysis, which uses restricted maximum likelihood to obtain an estimation of the additive effect of common Aglafoline chemical information variants or “SNP-chip heritability”59. We conducted these analyses, focusing on depressive symptoms, stressful life events, and social support separately, to evaluate the unique genetic contribution to these phenotypes and the potential presence of gene-environment correlation. We also examined the genetic contribution to depressive symptoms after adjusting for each of these environmental exposures individually. These analyses were performed only in African Americans, as a power calculation indicated the Hispanic/Latino sample would be underpowered to detect SNP heritability estimates in the range reported in previous studies of European Americans. We also performed a bivariate REML analysis to determine the genetic correlation between depressive symptoms and 
these two environmental exposures62. Finally, to evaluate the strength of our findings given the skewed distribution of our outcome, we repeated the top GWAS and GWEIS tests of association using a non-parametric bootstrap. For the top GWAS SNPs, we fit a linear regression on 1000 bootstrap samples using the boot package in R63,64 and compared the effective sizes from the bootstrap samples to the betas obtained in the original analysis for each top SNP. For the top GWEIS SNPs, we fit linear regressions to 5000 datasets simulated under the null hypothesis65 and generated p-values for each top SNP. These p-values represent the number of betas that were more extreme than the beta obtained in the original analysis divided by 5000 replicates. A significant p-value therefore indicates that the GE interaction is significant at that level. Author Manuscript Author Manuscript Author Manuscript Author Manuscript Depress Anxiety. Author manuscript; available in PMC 2017 April 01. Dunn et al. Page 7 Results Discovery Sample: GWAS There were 7,179 African American and 3,138 Hispanic/Latina women in the analysis. See Supplemental PubMed ID:http://www.ncbi.nlm.nih.gov/pubmed/19856273 Author Manuscript Author Manuscript Author Manuscript Author Manuscript Depress Anxiety. Author manuscript; available in PMC 2017 April 01. Dunn et al. Page 8 . The Hispanic/Latina discovery and HCHS/SOL replication results were also highly concordant, with 72% of linear regression beta coefficients yie.Depressive symptoms were measured by a 10-item CES-D, social support was measured through the 12-item version of the Interpersonal Support Evaluation List58, and stressful life events measured through a composite measure designed to match the discovery sample. We also assessed top GWAS findings for both Hispanics and African Americans in the Cohorts for Heart and Aging Research in Genomic Epidemiology, which performed the largest meta-analysis GWAS of depressive symptoms to date using 17 European-ancestry population-based studies of older adults where depressive symptoms were measured through the CES-D6. Secondary Analyses We performed five secondary analyses. First, we conducted two sets of meta analyses to determine the degree to which the top GWAS SNPs obtained in African Americans also showed evidence of nominal association in Hispanics/Latinas and vice versa. Second, we reran the GWAS in each sample after additionally adjusting for both environmental exposures, as both stressful life events and social support were found to make large and unique contributions to the variance in depressive symptoms. Third, we performed an analysis using genome-wide complex trait analysis, which uses restricted maximum likelihood to obtain an estimation of the additive effect of common variants or “SNP-chip heritability”59. We conducted these analyses, focusing on depressive symptoms, stressful life events, and social support separately, to evaluate the unique genetic contribution to these phenotypes and the potential presence of gene-environment correlation. We also examined the genetic contribution to depressive symptoms after adjusting for each of these environmental exposures individually. These analyses were performed only in African Americans, as a power calculation indicated the Hispanic/Latino sample would be underpowered to detect SNP heritability estimates in the range reported in previous studies of European Americans. We also performed a bivariate REML analysis to determine the genetic correlation between depressive symptoms and these two 
environmental exposures62. Finally, to evaluate the strength of our findings given the skewed distribution of our outcome, we repeated the top GWAS and GWEIS tests of association using a non-parametric bootstrap. For the top GWAS SNPs, we fit a linear regression on 1000 bootstrap samples using the boot package in R63,64 and compared the effective sizes from the bootstrap samples to the betas obtained in the original analysis for each top SNP. For the top GWEIS SNPs, we fit linear regressions to 5000 datasets simulated under the null hypothesis65 and generated p-values for each top SNP. These p-values represent the number of betas that were more extreme than the beta obtained in the original analysis divided by 5000 replicates. A significant p-value therefore indicates that the GE interaction is significant at that level. Author Manuscript Author Manuscript Author Manuscript Author Manuscript Depress Anxiety. Author manuscript; available in PMC 2017 April 01. Dunn et al. Page 7 Results Discovery Sample: GWAS There were 7,179 African American and 3,138 Hispanic/Latina women in the analysis. See Supplemental PubMed ID:http://www.ncbi.nlm.nih.gov/pubmed/19856273 Author Manuscript Author Manuscript Author Manuscript Author Manuscript Depress Anxiety. Author manuscript; available in PMC 2017 April 01. Dunn et al. Page 8 . The Hispanic/Latina discovery and HCHS/SOL replication results were also highly concordant, with 72% of linear regression beta coefficients yie.