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 Weinberger, Cuie Sun, Jonathan Flint, Ariel Darvasi

Research output: Contribution to journalArticle

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 female-specific association between RELN and schizophrenia is one of the few examples of a replicated sex-specific genetic association in any disease.

Original languageEnglish (US)
JournalPLoS Genetics
Volume4
Issue number2
DOIs
StatePublished - Feb 2008
Externally publishedYes

Fingerprint

Schizophrenia
genome
Genome
gene
gender
Genes
genes
Population
Genome-Wide Association Study
relative risk
gender differences
Sex Characteristics
Introns
Single Nucleotide Polymorphism
introns
genotype
Genotype
DNA
schizophrenia
woman

ASJC Scopus subject areas

  • Genetics
  • Molecular Biology
  • Ecology, Evolution, Behavior and Systematics
  • Cancer Research
  • Genetics(clinical)

Cite this

Shifman, S., Johannesson, M., Bronstein, M., Chen, S. X., Collier, D. A., Craddock, N. J., ... Darvasi, A. (2008). Genome-wide association identifies a common variant in the reelin gene that increases the risk of schizophrenia only in women. PLoS Genetics, 4(2). https://doi.org/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. / Shifman, Sagiv; Johannesson, Martina; Bronstein, Michal; Chen, Sam X.; Collier, David A.; Craddock, Nicholas J.; Kendler, Kenneth S.; Li, Tao; O'Donovan, Michael; O'Neill, F. Anthony; Owen, Michael J.; Walsh, Dermot; Weinberger, Daniel; Sun, Cuie; Flint, Jonathan; Darvasi, Ariel.

In: PLoS Genetics, Vol. 4, No. 2, 02.2008.

Research output: Contribution to journalArticle

Shifman, S, Johannesson, M, Bronstein, M, Chen, SX, Collier, DA, Craddock, NJ, Kendler, KS, Li, T, O'Donovan, M, O'Neill, FA, Owen, MJ, Walsh, D, Weinberger, D, Sun, C, Flint, J & Darvasi, A 2008, 'Genome-wide association identifies a common variant in the reelin gene that increases the risk of schizophrenia only in women', PLoS Genetics, vol. 4, no. 2. https://doi.org/10.1371/journal.pgen.0040028
Shifman, Sagiv ; Johannesson, Martina ; Bronstein, Michal ; Chen, Sam X. ; Collier, David A. ; Craddock, Nicholas J. ; Kendler, Kenneth S. ; Li, Tao ; O'Donovan, Michael ; O'Neill, F. Anthony ; Owen, Michael J. ; Walsh, Dermot ; Weinberger, Daniel ; Sun, Cuie ; Flint, Jonathan ; Darvasi, Ariel. / Genome-wide association identifies a common variant in the reelin gene that increases the risk of schizophrenia only in women. In: PLoS Genetics. 2008 ; Vol. 4, No. 2.
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