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

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)33-40
Number of pages8
JournalAmerican Journal of Medical Genetics, Part B: Neuropsychiatric Genetics
Volume150
Issue number1
DOIs
StatePublished - 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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    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