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PLoS Genet. 2008 Feb;4(2):e28. doi: 10.1371/journal.pgen.0040028.

Genome-wide association identifies a common variant in the reelin gene that increases the risk of schizophrenia only in women.

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  • 1Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, United Kindgdom. sagiv@vms.huji.ac.il

Abstract

Sex differences in schizophrenia are well known, but their genetic basis has not been identified. We performed a genome-wide association scan for schizophrenia in an Ashkenazi Jewish population using DNA pooling. We found a female-specific association with rs7341475, a SNP in the fourth intron of the reelin (RELN) gene (p = 2.9 x 10(-5) in women), with a significant gene-sex effect (p = 1.8 x 10(-4)). We studied rs7341475 in four additional populations, totaling 2,274 cases and 4,401 controls. A significant effect was observed only in women, replicating the initial result (p = 2.1 x 10(-3) in women; p = 4.2 x 10(-3) for gene-sex interaction). Based on all populations the estimated relative risk of women carrying the common genotype is 1.58 (p = 8.8 x 10(-7); p = 1.6 x 10(-5) for gene-sex interaction). The female-specific association between RELN and schizophrenia is one of the few examples of a replicated sex-specific genetic association in any disease.

PMID:
18282107
[PubMed - indexed for MEDLINE]
PMCID:
PMC2242812
Free PMC Article
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