Ted to be included in studies for general research use. Data were downloaded from the database of Genotypes and Phenotypes. Phenotype Definition Depressive symptoms were assessed at enrollment using total scores from a six-item version of the Center for Epidemiological Studies of Depression Scale 33, a widely-used measure of depressive symptoms in epidemiological studies. The six-item CES-D captured core symptoms of depression in the past week, including anhedonia, depressed mood, and LY341495 Depress Anxiety. Author manuscript; available in PMC 2017 April 01. Dunn et al. Page 4 behavioral symptoms. The six item scale correlates highly with the full 20-item CES-D 32. Brief versions of the CES-D correlate highly in older adults with diagnoses of MDD obtained from structured interviews34. As CES-D scores in this population-based sample could have been influenced by antidepressant medication use, we used a nonparametric imputation algorithm developed in a previous GWAS of depressive symptoms6 to adjust the CES-D score of women taking antidepressants. This algorithm, which increased the CES-D score for all antidepressant users, was based on one used to adjust blood pressure for persons on antihypertensive medications35. We tested for statistical GE interaction with two UNC0642 web environmental exposures stressful life events and social support both of which were shown to correlate with depressive symptoms in WHI32 and numerous other studies36. These two social-environmental exposures were measured at enrollment, concurrently with depressive symptoms. Stressful life events were assessed using a scale modified from the Almeida County Study37,38, which asked women to indicate whether they had experienced 11 different major losses or traumatic events in the past year. Items were summed to create a total count of the number of past-year stressors among those with complete data on all stressors. Social support was assessed using nine items from the 19-item Medical Outcome Survey39. We summed across these items to obtain a measure for level of perceived social support. SNP Genotyping and Imputation Author Manuscript Author Manuscript Author Manuscript Author Manuscript All participants were genotyped using the Affymetrix 6.0 chip designed to human genome build 36. Genotyping, on all samples plus 2% blinded duplicates, was performed at Affymetrix, Inc., Santa Clara, CA. A total of 720,101 and 709,042 SNPs passed pre-imputation filters. Quality control procedures were performed at the Fred Hutchinson Cancer Research Center in Seattle, WA. As described elsewhere, the WHI GARNET Coordinating Center performed the imputation using the 1000 Genomes Interim reference panel and BEAGLE software version 3.3.141. Quality Control of SNPs and Samples In addition to the QC standards imposed by WHI, we additionally excluded SNPs with a MAF of 2 % or imputation quality score < r2=0.80. Population stratification was assessed by WHI investigators using a principal components analysis estimated by the program EIGENSTRAT42. A total of 61 genetic outliers were removed from the African American analysis based on their PCA scores. After QC, 10,771 women were available for analysis. Allele dosages, rather than hard-called or "best guess" genotypes were used for both the GWAS and GWEIS analyses. Depress Anxiety. Author manuscript; available in PMC 2017 April 01. Dunn et al. Page 5 Statistical Analyses Author Manuscript Author Manuscript Author Manuscript Author Manuscript PubMed ID:http://www.ncbi.nlm.nih.gov/pubmed/1985786 Replication GWAS Ana.Ted to be included in studies for general research use. Data were downloaded from the database of Genotypes and Phenotypes. Phenotype Definition Depressive symptoms were assessed at enrollment using total scores from a six-item version of the Center for Epidemiological Studies of Depression Scale 33, a widely-used measure of depressive symptoms in epidemiological studies. The six-item CES-D captured core symptoms of depression in the past week, including anhedonia, depressed mood, and Depress Anxiety. Author manuscript; available in PMC 2017 April 01. Dunn et al. Page 4 behavioral symptoms. The six item scale correlates highly with the full 20-item CES-D 32. Brief versions of the CES-D correlate highly in older adults with diagnoses of MDD obtained from structured interviews34. As CES-D scores in this population-based sample could have been influenced by antidepressant medication use, we used a nonparametric imputation algorithm developed in a previous GWAS of depressive symptoms6 to adjust the CES-D score of women taking antidepressants. This algorithm, which increased the CES-D score for all antidepressant users, was based on one used to adjust blood pressure for persons on antihypertensive medications35. We tested for statistical GE interaction with two environmental exposures stressful life events and social support both of which were shown to correlate with depressive symptoms in WHI32 and numerous other studies36. These two social-environmental exposures were measured at enrollment, concurrently with depressive symptoms. Stressful life events were assessed using a scale modified from the Almeida County Study37,38, which asked women to indicate whether they had experienced 11 different major losses or traumatic events in the past year. Items were summed to create a total count of the number of past-year stressors among those with complete data on all stressors. Social support was assessed using nine items from the 19-item Medical Outcome Survey39. We summed across these items to obtain a measure for level of perceived social support. SNP Genotyping and Imputation Author Manuscript Author Manuscript Author Manuscript Author Manuscript All participants were genotyped using the Affymetrix 6.0 chip designed to human genome build 36. Genotyping, on all samples plus 2% blinded duplicates, was performed at Affymetrix, Inc., Santa Clara, CA. A total of 720,101 and 709,042 SNPs passed pre-imputation filters. Quality control procedures were performed at the Fred Hutchinson Cancer Research Center in Seattle, WA. As described elsewhere, the WHI GARNET Coordinating Center performed the imputation using the 1000 Genomes Interim reference panel and BEAGLE software version 3.3.141. Quality Control of SNPs and Samples In addition to the QC standards imposed by WHI, we additionally excluded SNPs with a MAF of 2 % or imputation quality score < r2=0.80. Population stratification was assessed by WHI investigators using a principal components analysis estimated by the program EIGENSTRAT42. A total of 61 genetic outliers were removed from the African American analysis based on their PCA scores. After QC, 10,771 women were available for analysis. Allele dosages, rather than hard-called or "best guess" genotypes were used for both the GWAS and GWEIS analyses. Depress Anxiety. Author manuscript; available in PMC 2017 April 01. Dunn et al. Page 5 Statistical Analyses Author Manuscript Author Manuscript Author Manuscript Author Manuscript PubMed ID:http://www.ncbi.nlm.nih.gov/pubmed/1985786 Replication GWAS Ana.

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