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Gender differences in genetic linkage and association on 11p15 in obsessive–compulsive disorder families
Author(s) -
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.,
HoehnSaric R.,
Pinto A.,
Fyer A.J.,
Piacentini J.,
Pauls D.L.,
Bienvenu O.J.,
Riddle M.,
Shugart Y.Y.,
Liang K.Y.,
Nestadt G.
Publication year - 2008
Publication title -
american journal of medical genetics part b: neuropsychiatric genetics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.393
H-Index - 126
eISSN - 1552-485X
pISSN - 1552-4841
DOI - 10.1002/ajmg.b.30760
Subject(s) - linkage (software) , association (psychology) , obsessive compulsive , psychology , genetics , genetic linkage , genetic association , biology , clinical psychology , gene , genotype , single nucleotide polymorphism , psychotherapist
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. © 2008 Wiley‐Liss, Inc.