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Article: Common Variants on Xq28 Conferring Risk of Schizophrenia in Han Chinese

TitleCommon Variants on Xq28 Conferring Risk of Schizophrenia in Han Chinese
Authors
Issue Date2014
Citation
Schizophrenia Bulletin, 2014, v. 40 n. 4, p. 777-786 How to Cite?
AbstractSchizophrenia 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.
Persistent Identifierhttp://hdl.handle.net/10722/191483
PubMed Central ID
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorWong, HMEen_US
dc.contributor.authorSO, HCen_US
dc.contributor.authorLi, Men_US
dc.contributor.authorWang, Qen_US
dc.contributor.authorButler, WLen_US
dc.contributor.authorBASIL, Pen_US
dc.contributor.authorWU, HMen_US
dc.contributor.authorHui, TCKen_US
dc.contributor.authorCHOI, SCen_US
dc.contributor.authorSo, MTen_US
dc.contributor.authorGarcia-Barcelo, MMen_US
dc.contributor.authorMcAlonan, GMen_US
dc.contributor.authorChen, EYHen_US
dc.contributor.authorCheung, EFCen_US
dc.contributor.authorChan, RCKen_US
dc.contributor.authorPurcell, SMen_US
dc.contributor.authorCherny, SSen_US
dc.contributor.authorChen, RYLen_US
dc.contributor.authorLi, Ten_US
dc.contributor.authorSham, PCen_US
dc.date.accessioned2013-10-15T07:03:29Z-
dc.date.available2013-10-15T07:03:29Z-
dc.date.issued2014en_US
dc.identifier.citationSchizophrenia Bulletin, 2014, v. 40 n. 4, p. 777-786en_US
dc.identifier.urihttp://hdl.handle.net/10722/191483-
dc.description.abstractSchizophrenia 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.-
dc.languageengen_US
dc.relation.ispartofSchizophrenia Bulletinen_US
dc.titleCommon Variants on Xq28 Conferring Risk of Schizophrenia in Han Chineseen_US
dc.typeArticleen_US
dc.identifier.emailLi, M: mxli@hku.hken_US
dc.identifier.emailButler, WL: wbutler@hku.hken_US
dc.identifier.emailHui, TCK: ckhui@hku.hken_US
dc.identifier.emailSo, MT: jaymtso@hku.hken_US
dc.identifier.emailGarcia-Barcelo, MM: mmgarcia@hku.hken_US
dc.identifier.emailMcAlonan, GM: mcalonan@hkucc.hku.hken_US
dc.identifier.emailChen, EYH: eyhchen@hku.hken_US
dc.identifier.emailCherny, SS: cherny@hku.hken_US
dc.identifier.emailChen, RYL: rylchen@hkucc.hku.hken_US
dc.identifier.emailSham, PC: pcsham@hku.hken_US
dc.identifier.authorityLi, M=rp01722en_US
dc.identifier.authorityGarcia-Barcelo, MM=rp00445en_US
dc.identifier.authorityMcAlonan, GM=rp00475en_US
dc.identifier.authorityChen, EYH=rp00392en_US
dc.identifier.authorityCherny, SS=rp00232en_US
dc.identifier.authoritySham, PC=rp00459en_US
dc.identifier.doi10.1093/schbul/sbt104-
dc.identifier.pmid24043878-
dc.identifier.pmcidPMC4059435-
dc.identifier.scopuseid_2-s2.0-84899895669-
dc.identifier.hkuros226189en_US
dc.identifier.isiWOS:000338130300010-

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