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

S Shifman, M Johannesson, M Bronstein… - PLoS …, 2008 - journals.plos.org
S Shifman, M Johannesson, M Bronstein, SX Chen, DA Collier, NJ Craddock, KS Kendler
PLoS genetics, 2008journals.plos.org
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 …
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 female-specific association between RELN and schizophrenia is one of the few examples of a replicated sex-specific genetic association in any disease.
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