Identification of a functional 339 bp <italic>Alu</italic> insertion polymorphism in the schizophrenia-associated locus at 10q24.32

Abstract

Genome-wide association studies (GWAS) have identified multiple single nucleotide polymorphisms (SNPs) or small indels robustly associated with schizophrenia; however, the functional risk variations remain largely unknown. We investigated the 10q24.32 locus and discovered a 339 bp <i>Alu</i> insertion polymorphism (rs71389983) in complete linkage disequilibrium (LD) with the schizophrenia GWAS risk variant rs7914558. The presence of the <i>Alu</i> insertion at rs71389983 strongly repressed transcriptional activities in <i>in vitro</i> luciferase assays. This polymorphism may be a target for future mechanistic research. Our study also underlines the importance and necessity of considering previously underestimated <i>Alu</i> polymorphisms in future genetic studies of schizophrenia.