Archival ReportProteome-wide Association Study Provides Insights Into the Genetic Component of Protein Abundance in Psychiatric Disorders
Section snippets
GWASs Used in This Study
Genome-wide associations from four large-scale GWASs of psychiatric disorders were used in this study. The genome-wide associations of schizophrenia were from a recent study by Lam et al. (7). By combining samples from East Asian ancestry and European ancestry, Lam et al. conducted a large-scale GWAS of schizophrenia (56,418 cases and 78,818 controls) and identified 176 independent risk loci (7). The genome-wide summary statistics of bipolar disorder (20,352 cases and 31,358 controls) were from
PWASs Identified 61 Genes Whose Genetically Regulated Protein Abundance Levels in the Brain Were Associated With Risk of Psychiatric Disorders
We first performed PWASs (discovery stage) by integrating the Banner human brain pQTL data (n = 152) and GWASs of four psychiatric disorders (schizophrenia, bipolar disorder, depression, and ADHD). We identified 29 PWS (corrected by Bonferroni adjustment) genes for schizophrenia (Table 1 and Figure 1A) and 3 PWS genes each for bipolar disorder and depression (Tables S1 and S2; Figures 2A and 3A). No PWS genes were identified for ADHD in the Banner dataset (Figure 4A). To validate these results,
Discussion
In this study, we performed PWASs for four common psychiatric disorders by integrating human brain pQTL data and genome-wide associations. We identified 61 genes whose genetically regulated protein abundance levels in the human brain were associated with risk of four common psychiatric disorders. Of note, among these PWS genes, 30 genes (including 20 genes for schizophrenia, 7 genes for bipolar disorder, 1 gene for depression, and 2 genes for ADHD) were not nominated by the original GWASs,
Acknowledgments and Disclosures
This study was equally supported by the Distinguished Young Scientists grant of the Yunnan Province (Grant No. 202001AV070006 [to X-JL]) and the Innovative Research Team of Science and Technology Department of Yunnan Province (Grant No. 2019HC004 [to X-JL]). This work was also supported by the Western Light Innovative Research Team of Chinese Academy of Sciences and the National Nature Science Foundation of China (Grant Nos. 31970561 [to X-JL] and 81901361 [to JL]).
X-JL conceived, designed, and
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