Intergenic variants may predispose to major depression disorder through regulation of long non-coding RNA expression

Abstract

Genome-wide association (GWA) studies have identified numerous genetic variants for major depressive disorder (MDD) although most of the genetic variants are intergenic. It has been found that approximately 54% of long non-coding RNAs (lncRNAs) are located in the intergenic regions. We hypothesized that intergenic variants might be involved in the pathogenesis of MDD through regulating the expression of lncRNAs where these variants are located. In this study, several MDD-associated SNPs in three known intergenic lncRNAs were initially genotyped among 978 patients with MDD and 1176 controls, and the real-time PCR assay was performed to quantify the expression of LINC01108 and LINC00578 in peripheral blood cells from 20 MDD patients and 20 controls. The results showed that rs12526133 present in LINC01108 was strongly associated with MDD (χ²=11.68, P=6.3E-04), and LINC01108 expression was significantly higher in the patient group than in the control group (FC=1.90, P<0.001). The expression of LINC00998 was significantly lower in MDD patients than controls based on microarray analysis (FC=0.11, P<0.001), so that its tag SNPs were genotyped and rs2272260 in LINC00998 was found to be associated with MDD (χ²=26.39, P=2.8E-07). This work suggests that non-coding variants may play an important role in conferring risk of MDD.

Keywords: GWAS; Intergenic variant; Long non-coding RNA; Major depression disorder.