TY - JOUR
T1 - Genome-wide association identifies a common variant in the reelin gene that increases the risk of schizophrenia only in women
AU - Shifman, Sagiv
AU - Johannesson, Martina
AU - Bronstein, Michal
AU - Chen, Sam X.
AU - Collier, David A.
AU - Craddock, Nicholas J.
AU - Kendler, Kenneth S.
AU - Li, Tao
AU - O'Donovan, Michael
AU - O'Neill, F. Anthony
AU - Owen, Michael J.
AU - Walsh, Dermot
AU - Weinberger, Daniel R.
AU - Sun, Cuie
AU - Flint, Jonathan
AU - Darvasi, Ariel
PY - 2008/2
Y1 - 2008/2
N2 - 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.
AB - 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.
UR - https://www.scopus.com/pages/publications/40149105889
U2 - 10.1371/journal.pgen.0040028
DO - 10.1371/journal.pgen.0040028
M3 - ???researchoutput.researchoutputtypes.contributiontojournal.article???
C2 - 18282107
AN - SCOPUS:40149105889
SN - 1553-7390
VL - 4
JO - PLoS Genetics
JF - PLoS Genetics
IS - 2
ER -