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- Title
Genome-Wide Association Identifies a Common Variant in the Reelin Gene That Increases the Risk of Schizophrenia Only in Women.
- Authors
Shifman, Sagiv; Johannesson, Martina; Bronstein, Michal; Chen, Sam X.; Collier, David A.; Craddock, Nicholas J.; Kendler, Kenneth S.; Tao Li; O'Donovan, Michael; O'Neill, F. Anthony; Owen, Michael J.; Walsh, Dermot; Weinberger, Daniel R.; Cuie Sun; Flint, Jonathan; Darvasi, Ariel
- 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 × 10-5 in women), with a significant gene-sex effect (p = 1.8 × 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 =2.1×10-3 in women; p=4.2×10-3 for gene-sex interaction). Based on all populations the estimated relative risk of women carrying the common genotype is 1.58 (p = 8.8 × 10-7; p = 1.6 × 10-5 for gene-sex interaction). The femalespecific association between RELN and schizophrenia is one of the few examples of a replicated sex-specific genetic association in any disease.
- Subjects
GENETIC research; SCHIZOPHRENIA; SEX differences (Biology); GENOMES; WOMEN'S health
- Publication
PLoS Genetics, 2008, Vol 4, Issue 2, p1
- ISSN
1553-7390
- Publication type
Article
- DOI
10.1371/journal.pgen.0040028