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: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

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

^*Corresponding author for this work

Department of Genetics

Research output: Contribution to journal › Article › peer-review

293 Scopus citations

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 language	English
Journal	PLoS Genetics
Volume	4
Issue number	2
DOIs	https://doi.org/10.1371/journal.pgen.0040028
State	Published - Feb 2008

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Shifman, S., Johannesson, M., Bronstein, M., Chen, S. X., Collier, D. A., Craddock, N. J., Kendler, K. S., Li, T., O'Donovan, M., O'Neill, F. A., Owen, M. J., Walsh, D., Weinberger, D. R., 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, 4(2). https://doi.org/10.1371/journal.pgen.0040028

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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 × 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.",

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

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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, DR, 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

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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.

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

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