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Chunk #2 — Results — Replication PWAS of depression

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Brain proteome-wide association study implicates novel proteins in depression pathogenesis.
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To increase confidence in our findings, we performed a replication PWAS of depression using proteomes and GWAS not included in our discovery analysis. The replication human brain proteomes were generated from the dPFC of 152 participants of European descent recruited by Banner Sun Health Research Institute23. They included 8,168 proteins after quality control and 1,139 of these had significant SNP-based heritability (p-value <0.01) and were included in the replication PWAS. Notably, there was a high degree of reproducibility of the protein weights estimated by FUSION between the discovery and replication proteomic datasets with a mean correlation of 0.79 and median of 0.85 (Supplementary Table 3). We integrated the replication proteomes with an independent depression GWAS of 23andMe participants of European descent (N=307,354) from Hyde et al21 to perform a replication PWAS of depression using FUSION (Supplementary Table 4). Due to the stochastic nature of high throughput proteomic sequencing, the replication proteomes profiled 17 of the 19 proteins identified in the discovery PWAS. However, only 13 of these 17 proteins were heritable, with SNP-based heritability p<0.01, and were part of the