Gender differences in genetic linkage and association on 11p15 in obsessive-compulsive disorder families

Y. Wang; J. F. Samuels; Y. C. Chang; M. A. Grados; B. D. Greenberg; J. A. Knowles; J. T. McCracken; S. L. Rauch; D. L. Murphy; S. A. Rasmussen; B. Cullen; R. Hoehn-Saric; A. Pinto; A. J. Fyer; J. Piacentini; D. L. Pauls; O. J. Bienvenu; M. Riddle; Y. Y. Shugart; K. Y. Liang; G. Nestadt

doi:10.1002/ajmg.b.30760

Gender differences in genetic linkage and association on 11p15 in obsessive-compulsive disorder families

Y. Wang, J. F. Samuels, Y. C. Chang, M. A. Grados, B. D. Greenberg, J. A. Knowles, J. T. McCracken, S. L. Rauch, D. L. Murphy, S. A. Rasmussen, B. Cullen, R. Hoehn-Saric, A. Pinto, A. J. Fyer, J. Piacentini, D. L. Pauls, O. J. Bienvenu, M. Riddle, Y. Y. Shugart, K. Y. LiangG. Nestadt

School of Medicine

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

23 Scopus citations

Abstract

Several clinical and genetic studies have reported gender differences in obsessive-compulsive disorder (OCD). Previously, we conducted a linkage genome scan using multipoint allele-sharing methods to test for linkage in 219 families participating in the OCD Collaborative Genetics Study. When these families were stratified by proband's gender, suggestive linkage to chromosome 11p15 at marker D11S2362 (KAC_all = 2.92, P = 0.00012) was detected in families with male probands, but not in the ones with female probands. We have since conducted fine mapping with a denser microsatellite marker panel in the region of 11p15, and detected a significant linkage signal at D11S4146 (KAC _all = 5.08, P < 0.00001) in the families of male probands. Subsequently, 632 SNPs were genotyped spanning a 4.0 Mb region of the 1 LOD unit interval surrounding the linkage peak in the original families and an additional 165 families. Six SNPs were associated with OCD (P < 0.001): two SNPs were identified when all the families were included, and four SNPs only in male proband families. No SNP showed significant association with the OCD phenotype only in the families with a female proband. The results suggest a possible gender effect in the etiology of OCD.

Original language	English (US)
Pages (from-to)	33-40
Number of pages	8
Journal	American Journal of Medical Genetics, Part B: Neuropsychiatric Genetics
Volume	150
Issue number	1
DOIs	https://doi.org/10.1002/ajmg.b.30760
State	Published - Jan 5 2009

Keywords

Association
Gender
Genetics
Linkage
OCD

ASJC Scopus subject areas

Genetics(clinical)
Psychiatry and Mental health
Cellular and Molecular Neuroscience

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10.1002/ajmg.b.30760

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Wang, Y., Samuels, J. F., Chang, Y. C., Grados, M. A., Greenberg, B. D., Knowles, J. A., McCracken, J. T., Rauch, S. L., Murphy, D. L., Rasmussen, S. A., Cullen, B., Hoehn-Saric, R., Pinto, A., Fyer, A. J., Piacentini, J., Pauls, D. L., Bienvenu, O. J., Riddle, M., Shugart, Y. Y., ... Nestadt, G. (2009). Gender differences in genetic linkage and association on 11p15 in obsessive-compulsive disorder families. American Journal of Medical Genetics, Part B: Neuropsychiatric Genetics, 150(1), 33-40. https://doi.org/10.1002/ajmg.b.30760

Wang, Y, Samuels, JF, Chang, YC, Grados, MA, Greenberg, BD, Knowles, JA, McCracken, JT, Rauch, SL, Murphy, DL, Rasmussen, SA, Cullen, B, Hoehn-Saric, R, Pinto, A, Fyer, AJ, Piacentini, J, Pauls, DL, Bienvenu, OJ, Riddle, M, Shugart, YY, Liang, KY & Nestadt, G 2009, 'Gender differences in genetic linkage and association on 11p15 in obsessive-compulsive disorder families', American Journal of Medical Genetics, Part B: Neuropsychiatric Genetics, vol. 150, no. 1, pp. 33-40. https://doi.org/10.1002/ajmg.b.30760

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title = "Gender differences in genetic linkage and association on 11p15 in obsessive-compulsive disorder families",

abstract = "Several clinical and genetic studies have reported gender differences in obsessive-compulsive disorder (OCD). Previously, we conducted a linkage genome scan using multipoint allele-sharing methods to test for linkage in 219 families participating in the OCD Collaborative Genetics Study. When these families were stratified by proband's gender, suggestive linkage to chromosome 11p15 at marker D11S2362 (KACall = 2.92, P = 0.00012) was detected in families with male probands, but not in the ones with female probands. We have since conducted fine mapping with a denser microsatellite marker panel in the region of 11p15, and detected a significant linkage signal at D11S4146 (KAC all = 5.08, P < 0.00001) in the families of male probands. Subsequently, 632 SNPs were genotyped spanning a 4.0 Mb region of the 1 LOD unit interval surrounding the linkage peak in the original families and an additional 165 families. Six SNPs were associated with OCD (P < 0.001): two SNPs were identified when all the families were included, and four SNPs only in male proband families. No SNP showed significant association with the OCD phenotype only in the families with a female proband. The results suggest a possible gender effect in the etiology of OCD.",

keywords = "Association, Gender, Genetics, Linkage, OCD",

author = "Y. Wang and Samuels, {J. F.} and Chang, {Y. C.} and Grados, {M. A.} and Greenberg, {B. D.} and Knowles, {J. A.} and McCracken, {J. T.} and Rauch, {S. L.} and Murphy, {D. L.} and Rasmussen, {S. A.} and B. Cullen and R. Hoehn-Saric and A. Pinto and Fyer, {A. J.} and J. Piacentini and Pauls, {D. L.} and Bienvenu, {O. J.} and M. Riddle and Shugart, {Y. Y.} and Liang, {K. Y.} and G. Nestadt",

note = "Funding Information: This work was supported by NSTIP strategic program number (12-INF2820-02) in the Kingdom of Saudi Arabia. The authors would like to thank all personnel involved in this work.",

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AU - Wang, Y.

AU - Samuels, J. F.

AU - Chang, Y. C.

AU - Grados, M. A.

AU - Greenberg, B. D.

AU - Knowles, J. A.

AU - McCracken, J. T.

AU - Rauch, S. L.

AU - Murphy, D. L.

AU - Rasmussen, S. A.

AU - Cullen, B.

AU - Hoehn-Saric, R.

AU - Pinto, A.

AU - Fyer, A. J.

AU - Piacentini, J.

AU - Pauls, D. L.

AU - Bienvenu, O. J.

AU - Riddle, M.

AU - Shugart, Y. Y.

AU - Liang, K. Y.

AU - Nestadt, G.

N1 - Funding Information: This work was supported by NSTIP strategic program number (12-INF2820-02) in the Kingdom of Saudi Arabia. The authors would like to thank all personnel involved in this work.

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N2 - Several clinical and genetic studies have reported gender differences in obsessive-compulsive disorder (OCD). Previously, we conducted a linkage genome scan using multipoint allele-sharing methods to test for linkage in 219 families participating in the OCD Collaborative Genetics Study. When these families were stratified by proband's gender, suggestive linkage to chromosome 11p15 at marker D11S2362 (KACall = 2.92, P = 0.00012) was detected in families with male probands, but not in the ones with female probands. We have since conducted fine mapping with a denser microsatellite marker panel in the region of 11p15, and detected a significant linkage signal at D11S4146 (KAC all = 5.08, P < 0.00001) in the families of male probands. Subsequently, 632 SNPs were genotyped spanning a 4.0 Mb region of the 1 LOD unit interval surrounding the linkage peak in the original families and an additional 165 families. Six SNPs were associated with OCD (P < 0.001): two SNPs were identified when all the families were included, and four SNPs only in male proband families. No SNP showed significant association with the OCD phenotype only in the families with a female proband. The results suggest a possible gender effect in the etiology of OCD.

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Gender differences in genetic linkage and association on 11p15 in obsessive-compulsive disorder families

Abstract

Keywords

ASJC Scopus subject areas

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