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Schizophr Bull. 2014 Jul;40(4):777-86. doi: 10.1093/schbul/sbt104. Epub 2013 Sep 16.

Common variants on Xq28 conferring risk of schizophrenia in Han Chinese.

Author information

1
Department of Psychiatry, The University of Hong Kong, Hong Kong, China; Co-first authors.
2
Department of Psychiatry, The University of Hong Kong, Hong Kong, China; Centre for Genomic Sciences, The University of Hong Kong, Hong Kong, China;
3
The Mental Health Centre and Psychiatric Laboratory, West China Hospital, Sichuan University, Chengdu, Sichuan, China;
4
Department of Psychiatry, The University of Hong Kong, Hong Kong, China; MRC Social Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, King's College London, London, UK;
5
Department of Psychiatry, The University of Hong Kong, Hong Kong, China;
6
Department of Surgery, The University of Hong Kong, Hong Kong, China;
7
Centre for Genomic Sciences, The University of Hong Kong, Hong Kong, China; Department of Surgery, The University of Hong Kong, Hong Kong, China;
8
Department of Forensic and Neurodevelopmental Sciences, Institute of Psychiatry, King's College London, UK;
9
Castle Peak Hospital, Hong Kong, China;
10
Institute of Psychology, Chinese Academy of Sciences, Beijing, China;
11
Division of Psychiatric Genomics, Mount Sinai School of Medicine, New York;
12
Department of Psychiatry, The University of Hong Kong, Hong Kong, China; Centre for Genomic Sciences, The University of Hong Kong, Hong Kong, China; State Key Laboratory in Brain and Cognitive Sciences, The University of Hong Kong, Hong King, China;
13
Department of Psychiatry, The University of Hong Kong, Hong Kong, China; Centre for Genomic Sciences, The University of Hong Kong, Hong Kong, China; State Key Laboratory in Brain and Cognitive Sciences, The University of Hong Kong, Hong King, China; pcsham@hku.hk.

Abstract

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.

KEYWORDS:

ARHGAP4; Han Chinese; MECP2; RENBP; genome-wide association study; schizophrenia

PMID:
24043878
PMCID:
PMC4059435
DOI:
10.1093/schbul/sbt104
[Indexed for MEDLINE]
Free PMC Article

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