Genetic association and meta-analysis of a schizophrenia GWAS variant rs10489202 in East Asian populations

Abstract

Previous genome-wide association studies (GWAS) suggest that rs10489202 in the intron of MPC2 (mitochondrial pyruvate carrier 2) is a risk locus for schizophrenia in Han Chinese populations. To validate this discovery, we conducted a replication analysis in an independent case-control sample of Han Chinese ancestry (437 cases and 2031 controls), followed by a meta-analytic investigation in multiple East Asian samples. In the replication analysis, rs10489202 showed marginal association with schizophrenia (two-tailed P = 0.071, OR = 1.192 for T allele); in the meta-analysis using a total of 14,340 cases and 20,349 controls from ten East Asian samples, rs10489202 was genome-wide significantly associated with schizophrenia (two-tailed P = 3.39 × 10^–10, OR = 1.161 for T allele, under the fixed-effect model). We then performed an explorative investigation of the association between this SNP and bipolar disorder, as well as a major depressive disorder, and the schizophrenia-predisposing allele was associated with an increased risk of major depressive disorder in East Asians (two-tailed P = 2.49 × 10^–2, OR = 1.103 for T allele). Furthermore, expression quantitative trait loci (eQTL) analysis in lymphoblastoid cell lines from East Asian donors (N = 85 subjects) revealed that rs10489202 was specifically and significantly associated with the expression of TIPRL gene (P = 5.67 × 10^–4). Taken together, our data add further support for the genetic involvement of this genomic locus in the susceptibility to schizophrenia in East Asian populations, and also provide preliminary evidence for the underlying molecular mechanisms.