PLoS Genetics (Feb 2008)

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

  • Sagiv Shifman,
  • Martina Johannesson,
  • Michal Bronstein,
  • Sam X Chen,
  • David A Collier,
  • Nicholas J Craddock,
  • Kenneth S Kendler,
  • Tao Li,
  • Michael O'Donovan,
  • F Anthony O'Neill,
  • Michael J Owen,
  • Dermot Walsh,
  • Daniel R Weinberger,
  • Cuie Sun,
  • Jonathan Flint,
  • Ariel Darvasi

DOI
https://doi.org/10.1371/journal.pgen.0040028
Journal volume & issue
Vol. 4, no. 2
p. e28

Abstract

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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.