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Chunk #0 — Results — Discovery PWAS of depression

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Brain proteome-wide association study implicates novel proteins in depression pathogenesis.
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We integrated reference human brain proteomes with the latest depression GWAS results10 to perform a PWAS of depression using the FUSION pipeline16. The human brain proteomes were generated from the dorsolateral prefrontal cortex (dPFC) of 376 participants of European descent of the Religious Order Study and Rush Memory and Aging Project (ROS/MAP)13,22. They included 8356 proteins after quality control and 1468 of these had significant SNP-based heritability (p-value <0.01) and were included in the PWAS. The depression GWAS summary statistics were from 500,199 participants of European descent that were not 23andMe,Inc. participants from the latest Howard et al depression GWAS10. The discovery PWAS identified 24 genes whose cis-regulated brain protein abundances were associated with depression at FDR q<0.05 (Figure 1, Table 1, Supplementary Table 1). Each of these 24 genes is located >500 kb apart.