| Abstract |
schizophreniais a highly heritable, severe psychiatric disorder affecting approximately 1% of the world population. A substantial portion of heritability is still unexplained and the pathophysiology ofschizophreniaremains to be elucidated. To identify moreschizophreniasusceptibility loci, we performed a genome-wide association study (GWAS) on 498 patients withschizophreniaand 2025 controls from the Han Chinese population, and a follow-up study on 1027 cases and 1005 controls. In the follow-up study, we included 384 single nucleotide polymorphisms (SNPs) which were selected from the top hits in our GWAS (130 SNPs) and from previously implicated loci forschizophreniabased on the SZGene database, NHGRI GWAS Catalog, copy number variation studies, GWAS meta-analysis results from the international Psychiatric Genomics Consortium (PGC) and candidate genes from plausible biological pathways (254 SNPs). Within the chromosomal region Xq28, SNP rs2269372 inRENBPachieved genome-wide significance with a combined P value of 3.98 � 10(-8) (OR of allele A = 1.31). SNPs with suggestive P values were identified within 2 genes that have been previously implicated inschizophreniaMECP2 (rs2734647 P组合d = 8.78 � 10(-7), OR = 1.28; rs2239464, P combined = 6.71 � 10(-6), OR = 1.26) and ARHGAP4 (rs2269368, P combined = 4.74 � 10(-7), OR = 1.25). In addition, the patient sample in our follow-up study showed a significantly greater burden for pre-defined risk alleles based on the SNPs selected than the controls. This indicates the existence ofschizophreniasusceptibility loci among the SNPs we selected. This also further supports multigenic inheritance inschizophrenia. Our findings identified a newschizophreniasusceptibility locus on Xq28, which harbor the genesRENBP, MECP2, and ARHGAP4. |