Genome-wide Association Identifies a Common Variant in the Reelin Gene That Increases the Risk of Schizophrenia Only in Women

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

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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Alleles
  • Asian Continental Ancestry Group / genetics
  • Case-Control Studies
  • Cell Adhesion Molecules, Neuronal / genetics*
  • European Continental Ancestry Group / genetics
  • Extracellular Matrix Proteins / genetics*
  • Female
  • Gene Frequency
  • Genetic Predisposition to Disease
  • Genetic Variation*
  • Genome, Human
  • Humans
  • Introns
  • Jews / genetics
  • Male
  • Middle Aged
  • Nerve Tissue Proteins / genetics*
  • Odds Ratio
  • Polymorphism, Single Nucleotide
  • Risk Factors
  • Schizophrenia / etiology
  • Schizophrenia / genetics*
  • Serine Endopeptidases / genetics*
  • Sex Characteristics

Substances

  • Cell Adhesion Molecules, Neuronal
  • Extracellular Matrix Proteins
  • Nerve Tissue Proteins
  • Serine Endopeptidases
  • reelin protein