title: Genome-wide association identifies a common variant in the reelin gene that increases the risk of schizophrenia only in women.
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.
authors.affiliation: Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, United Kindgdom. sagiv@vms.huji.ac.il
authors.forename: Sagiv
authors.initials: S
authors.lastname: Shifman
authors.forename: Martina
authors.initials: M
authors.lastname: Johannesson
authors.forename: Michal
authors.initials: M
authors.lastname: Bronstein
authors.forename: Sam X
authors.initials: SX
authors.lastname: Chen
authors.forename: David A
authors.initials: DA
authors.lastname: Collier
authors.forename: Nicholas J
authors.initials: NJ
authors.lastname: Craddock
authors.forename: Kenneth S
authors.initials: KS
authors.lastname: Kendler
authors.forename: Tao
authors.initials: T
authors.lastname: Li
authors.forename: Michael
authors.initials: M
authors.lastname: O'Donovan
authors.forename: F Anthony
authors.initials: FA
authors.lastname: O'Neill
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Owen
authors.forename: Dermot
authors.initials: D
authors.lastname: Walsh
authors.forename: Daniel R
authors.initials: DR
authors.lastname: Weinberger
authors.forename: Cuie
authors.initials: C
authors.lastname: Sun
authors.forename: Jonathan
authors.initials: J
authors.lastname: Flint
authors.forename: Ariel
authors.initials: A
authors.lastname: Darvasi
mesh_terms: D000328:Adult; D000483:Alleles; D044466:Asian People / Q000235:genetics; D016022:Case-Control Studies; D015816:Cell Adhesion Molecules, Neuronal / Q000235:genetics*; D016326:Extracellular Matrix Proteins / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D015894:Genome, Human; D006801:Humans; D007438:Introns; D007585:Jews / Q000235:genetics; D008297:Male; D008875:Middle Aged; D009419:Nerve Tissue Proteins / Q000235:genetics*; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide; D000091042:Reelin Protein; D012307:Risk Factors; D012559:Schizophrenia / Q000209:etiology / Q000235:genetics*; D012697:Serine Endopeptidases / Q000235:genetics*; D012727:Sex Characteristics; D044465:White People / Q000235:genetics
chemical_list: D015816:Cell Adhesion Molecules, Neuronal; D016326:Extracellular Matrix Proteins; D009419:Nerve Tissue Proteins; D000091042:Reelin Protein; C000717127:RELN protein, human; D012697:Serine Endopeptidases