Common Variants on Xq28 Conferring Risk of Schizophrenia in Han Chinese
| Autor: | Basil Paul, Maria-Mercè Garcia-Barceló, Ronald R. L. Chen, Stacey S. Cherny, Grainne M. McAlonan, Man-Ting So, Tomy C. K. Hui, Amy W. Butler, Siu-Chung Choi, Eric F.C. Cheung, Shaun Purcell, Pak C. Sham, Miaoxin Li, Tao Li, Quang Wang, Hon-Cheong So, Raymond C.K. Chan, Emily H. M. Wong, Eric Y.H. Chen, Hei-Man Wu |
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| Jazyk: | angličtina |
| Rok vydání: | 2013 |
| Předmět: |
Male
Candidate gene China Methyl-CpG-Binding Protein 2 Schizophrenia (object-oriented programming) Population Single-nucleotide polymorphism Genome-wide association study Biology Polymorphism Single Nucleotide Asian People Humans Genetic Predisposition to Disease Copy-number variation education Alleles Genetic association Genetics education.field_of_study Chromosomes Human X GTPase-Activating Proteins Case-control study Genetic Variation Regular Article Psychiatry and Mental health Logistic Models Case-Control Studies Schizophrenia Female Carbohydrate Epimerases Carrier Proteins Genome-Wide Association Study |
| Popis: | Schizophrenia is a highly heritable, severe psychiatric disorder affecting approximately 1% of the world population. A substantial portion of heritability is still unexplained and the pathophysiology of schizophrenia remains to be elucidated. To identify more schizophrenia susceptibility loci, we performed a genome-wide association study (GWAS) on 498 patients with schizophrenia and 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 for schizophrenia based 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 in RENBP achieved 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 in schizophrenia, MECP2 (rs2734647, P combined = 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 of schizophrenia susceptibility loci among the SNPs we selected. This also further supports multigenic inheritance in schizophrenia. Our findings identified a new schizophrenia susceptibility locus on Xq28, which harbor the genes RENBP, MECP2, and ARHGAP4. © 2014 The Author. |
| Databáze: | OpenAIRE |
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