Integrating genetic regulation and schizophrenia-specific splicing quantitative expression with GWAS prioritizes novel risk genes for schizophrenia.

ABSTRACT: Alternative splicing (AS) plays a vital role in the pathogenesis of schizophrenia (SCZ). Previous studies have linked the genetic signals from genome-wide association studies (GWAS) with expression quantitative trait loci (eQTL), but the interplay with other genetic regulatory mechanisms, particularly splicing QTL (sQTL), remains unclear. Here, we constructed a comprehensive disease-specific sQTL map to provide genetic variants that could alter gene activity through RNA splicing in SCZ. We analyzed data from 539 SCZ patients, identifying a total of 24,810 significant sQTLs (FDR < 0.05) involving in AS events of 7083 unique genes. By combining this with a large-scale SCZ GWAS, we employed Mendelian randomization (MR) and colocalization analyses to pinpoint 27 significant risk genes with gen

SUBMITTER: Li X 

PROVIDER: S-EPMC12501019 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature