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Chunk #4 — Results — Primary analysis.

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Bi-ancestral depression GWAS in the Million Veteran Program and meta-analysis in >1.2 million individuals highlight new therapeutic directions.
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For the ICD code definition of major depressive disorder (see Online Methods for detailed diagnosis definitions), the phenotype with the most available data for the MVP cohort, we conducted a GWAS on 250,215 European individuals (83,810 cases). These MVP data were then included in a meta-analysis in METAL12 using inverse variance weighting with available depression GWAS summary statistics from cohorts of European-ancestry subjects (hereafter, “MDD-META”, Figure 1, Table 1): the PGC and the UK Biobank,10 FinnGen (http://r2.finngen.fi/pheno/F5_MOOD), and 23andMe,9 for a total of 1,154,267 subjects of European ancestry (340,591 cases). We identified 223 independent significant SNPs at 178 genomic risk loci in the primary analysis of European ancestry (Figure 1). We also conducted a GWAS in the African American (AA) sample from MVP in 59,600 participants (25,843 cases). There were no genome-wide significant (GWS) findings from our primary analysis of MDD in African Americans, so we examined overlap with the 223 GWS SNPs from our primary MDD-META meta-analysis of European American ancestry. Of the 223 GWS SNPs from the primary analysis, 206 were available following QC in the AA cohort.