| Proteome-wide association study provides insights into the genetic component of protein abundance in psychiatric disorders |
| 2021-12-03
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Proteome-wide association study provides insights into the genetic component of protein abundance in psychiatric disorders. Biol Psychiatry, 2021.Title:Proteome-wide association study provides insights into the genetic component of protein abundance in psychiatric disorders. Author:Liu JW, Li XY, Luo XJ. Publication Name:Biol Psychiatry Pub Year: 2021 Doi: 10.1016/j.biopsych.2021.06.022. IF: 13.382 Abstract: BACKGROUND: Genome-wide association studies have identified multiple risk variants for psychiatric disorders. Nevertheless, how the risk variants confer risk of psychiatric disorders remains largely unknown.
METHODS: We performed proteome-wide association studies to identify genes whose cis-regulated protein abundance change in the human brain were associated with psychiatric disorders.
RESULTS: By integrating genome-wide associations of four common psychiatric disorders and two independent brain proteomes (n= 376 and n= 152, respectively) from the dorsolateral prefrontal cortex, we identified 61 genes (including 48 genes for schizophrenia, 12 genes for bipolar disorder, 5 genes for depression, and 2 genes for attention-deficit/hyperactivity disorder) whose genetically regulated protein abundance levels were associated with risk of psychiatric disorders. Comparison with transcriptome-wide association studies identified 18 overlapping genes that showed significant associations with psychiatric disorders at both proteome-wide and transcriptome-wide levels, suggesting that genetic risk variants likely confer risk of psychiatric disorders by regulating messenger RNA expression and protein abundance of these genes.
CONCLUSIONS: Our study not only provides new insights into the genetic component of protein abundance in psychiatric disorders but also highlights several high-confidence risk proteins (including CNNM2 and CTNND1) for schizophrenia and depression. These high-confidence risk proteins represent promising therapeutic targets for future drug development. |
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