A causal coding variant regulating alternative splicing of <i>DOC2A</i> at 16p.11.2 GWAS locus influences susceptibility to schizophrenia.

ABSTRACT: Although genome-wide association studies (GWASs) have identified many schizophrenia-associated variants, their biological mechanisms remain unclear. Using transcriptomic data from human brain tissues, we performed splicing quantitative trait locus (sQTL) analyses of schizophrenia-associated single-nucleotide polymorphisms and identified more than 17,000 sQTLs linked to previously unidentified splicing junctions. Functional prioritization and experimental validation highlighted the synonymous variant rs3935873 within the 16p11.2 GWAS locus strongly associated with an unannotated isoform DOC2A^{∆Val217-Pro218}. rs3935873 was significantly associated with hippocampal volume, and hippocampal overexpression of DOC2A^{∆Val217-Pro218} in mice recapitulated sch

SUBMITTER: Zhou D 

PROVIDER: S-EPMC12810641 | biostudies-literature | 2026 Jan

REPOSITORIES: biostudies-literature