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Brain Proteome-Wide Association Study Identifies Candidate Genes that Regulate Protein Abundance Associated with Post-Traumatic Stress Disorder

Authors :
Zhen Zhang
Peilin Meng
Huijie Zhang
Yumeng Jia
Yan Wen
Jingxi Zhang
Yujing Chen
Chun’e Li
Chuyu Pan
Shiqiang Cheng
Xuena Yang
Yao Yao
Li Liu
Feng Zhang
Source :
Genes; Volume 13; Issue 8; Pages: 1341
Publication Year :
2022
Publisher :
Multidisciplinary Digital Publishing Institute, 2022.

Abstract

Although previous genome-wide association studies (GWASs) on post-traumatic stress disorder (PTSD) have identified multiple risk loci, how these loci confer risk of PTSD remains unclear. Through the FUSION pipeline, we integrated two human brain proteome reference datasets (ROS/MAP and Banner) with the PTSD GWAS dataset, respectively, to conduct a proteome-wide association study (PWAS) analysis. Then two transcriptome reference weights (Rnaseq and Splicing) were applied to a transcriptome-wide association study (TWAS) analysis. Finally, the PWAS and TWAS results were investigated through brain imaging analysis. In the PWAS analysis, 8 and 13 candidate genes were identified in the ROS/MAP and Banner reference weight groups, respectively. Examples included ADK (pPWAS-ROS/MAP = 3.00 × 10−5) and C3orf18 (pPWAS-Banner = 7.07 × 10−31). Moreover, the TWAS also detected multiple candidate genes associated with PTSD in two different reference weight groups, including RIMS2 (pTWAS-Splicing = 3.84 × 10−2), CHMP1A (pTWAS-Rnaseq = 5.09 × 10−4), and SIRT5 (pTWAS-Splicing = 4.81 × 10−3). Further comparison of the PWAS and TWAS results in different populations detected the overlapping genes: MADD (pPWAS-Banner = 4.90 × 10−2, pTWAS-Splicing = 1.23 × 10−2) in the total population and GLO1(pPWAS-Banner = 4.89 × 10−3, pTWAS-Rnaseq = 1.41 × 10−3) in females. Brain imaging analysis revealed several different brain imaging phenotypes associated with MADD and GLO1 genes. Our study identified multiple candidate genes associated with PTSD in the proteome and transcriptome levels, which may provide new clues to the pathogenesis of PTSD.

Details

Language :
English
ISSN :
20734425
Database :
OpenAIRE
Journal :
Genes; Volume 13; Issue 8; Pages: 1341
Accession number :
edsair.doi.dedup.....257f2929a042dde2bdaf94ad756eb946
Full Text :
https://doi.org/10.3390/genes13081341