Prioritization of SCZ risk genes and SNPs

WZ Wendiao Zhang
MZ Ming Zhang
ZX Zhenhong Xu
HY Hongye Yan
HW Huimin Wang
JJ Jiamei Jiang
JW Juan Wan
BT Beisha Tang
CL Chunyu Liu
CC Chao Chen
QM Qingtuan Meng
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We collected the published data from TWAS811, MR-JTI15, and SMR2,10,12,13 analyses to prioritize SCZ risk genes with sufficient supporting evidence. We also checked whether the prioritized genes are located in SCZ risk-associated gene coexpression modules or differentially expressed in postmortem brains of SCZ patients.

To prioritize SCZ risk SNPs, we first collected the top SNPs from the TWAS data. We then retrieved SNPs in LD (r2 ≥ 0.6, European population genome) with the top SNPs. We prioritized candidate causal SNPs that likely affected gene expression in the brain using the following criteria: 1) candidate SNPs are eSNPs for the SCZ risk genes in the brain based on the BrainSeq25, GTEx24, or PsychENCODE eQTL data47; 2) SNPs are located within chromatin open regions based on ATAC-seq data from the PsychENCODE consortium; 3) SNPs are located in genomic regions predicted as enhancers or promoters in human brain tissues or neural cell cultures based on the Roadmap Epigenomics data23.

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