TY - JOUR
T1 - Replication study supports evidence for linkage to 9p24 in obsessive-compulsive disorder
AU - Willour, Virginia L.
AU - Shugart, Yin Yao
AU - Samuels, Jack
AU - Grados, Marco
AU - Cullen, Bernadette
AU - Bienvenu, O. Joseph
AU - Wang, Ying
AU - Liang, Kung Yee
AU - Valle, David
AU - Hoehn-Saric, Rudolf
AU - Riddle, Mark
AU - Nestadt, Gerald
N1 - Funding Information:
Our research was supported by grant R01 MH50214 from the National Institute of Mental Health (to G.N.); by grant RR00052 from the Division of Research Resources General Clinical Research Centers, National Institutes of Health; by funds from the Department of Epidemiology, Bloomberg School of Public Health, Johns Hopkins University (to Y.Y.S.); and by a grant from the National Alliance for Research on Schizophrenia and Depression (to V.L.W.). We thank the many families for participating in the study; J. Raymond DePaulo, Jr. (Department of Psychiatry and Behavioral Sciences at Johns Hopkins University), for financial support of V.L.W.; Edwin Cook, Gregory Hanna, and Jeremy Veenstra-VanderWeele for providing access to their primer sequences; Jennifer Hahn, Malgorzata Lamacz, Karan Lamb, Yung-Mei Leong, Tracey Lichner, James Luke, Dan McLeod, David Wellen, and Ruth Zitner for conducting clinical evaluations; Laura Eisen, Sandra Hensley, and Krista Vermillion for their efforts in coordinating the study; and Tyra Diggs, Jennifer Chellis, Yuqing Huo, and Amanda Rebert for technical assistance.
PY - 2004/9
Y1 - 2004/9
N2 - Obsessive-compulsive disorder (OCD) is a severe psychiatric illness that is characterized by intrusive and senseless thoughts and impulses (obsessions) and by repetitive behaviors (compulsions). Family, twin, and segregation studies support the presence of both genetic and environmental susceptibility factors, and the only published genome scan for OCD identified a candidate region on 9p24 at marker D9S288 that met criteria for suggestive significance (Hanna et al. 2002). In an attempt to replicate this finding, we genotyped 50 pedigrees with OCD, using microsatellite markers spanning the 9p24 candidate region, and analyzed the data, using parametric and nonparametric linkage analyses under both a narrow phenotype model (DSM-IV OCD definite; 41 affected sib pairs) and a broad phenotype model (DSM-IV OCD definite and probable; 50 affected sib pairs). Similar to what was described by Hanna et al. (2002), our strongest findings came with the dominant parameters and the narrow phenotype model: the parametric signal peaked at marker D9S1792 with an HLOD of 2.26 (α = 0.59), and the nonparametric linkage signal (NPL) peaked at marker D9S1813 with an NPL of 2.52 (P = .006). These findings are striking in that D9S1813 and D9S1792 lie within 0.5 cM (<350 kb) of the original 9p24 linkage signal at D9S288; furthermore, pedigree-based association analyses also implicated the 9p24 candidate region by identifying two markers (D9S288 and GATA62F03) with modest evidence (P = .046 and .02, respectively) for association.
AB - Obsessive-compulsive disorder (OCD) is a severe psychiatric illness that is characterized by intrusive and senseless thoughts and impulses (obsessions) and by repetitive behaviors (compulsions). Family, twin, and segregation studies support the presence of both genetic and environmental susceptibility factors, and the only published genome scan for OCD identified a candidate region on 9p24 at marker D9S288 that met criteria for suggestive significance (Hanna et al. 2002). In an attempt to replicate this finding, we genotyped 50 pedigrees with OCD, using microsatellite markers spanning the 9p24 candidate region, and analyzed the data, using parametric and nonparametric linkage analyses under both a narrow phenotype model (DSM-IV OCD definite; 41 affected sib pairs) and a broad phenotype model (DSM-IV OCD definite and probable; 50 affected sib pairs). Similar to what was described by Hanna et al. (2002), our strongest findings came with the dominant parameters and the narrow phenotype model: the parametric signal peaked at marker D9S1792 with an HLOD of 2.26 (α = 0.59), and the nonparametric linkage signal (NPL) peaked at marker D9S1813 with an NPL of 2.52 (P = .006). These findings are striking in that D9S1813 and D9S1792 lie within 0.5 cM (<350 kb) of the original 9p24 linkage signal at D9S288; furthermore, pedigree-based association analyses also implicated the 9p24 candidate region by identifying two markers (D9S288 and GATA62F03) with modest evidence (P = .046 and .02, respectively) for association.
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U2 - 10.1086/423899
DO - 10.1086/423899
M3 - Article
C2 - 15272418
AN - SCOPUS:4143118848
SN - 0002-9297
VL - 75
SP - 508
EP - 513
JO - American journal of human genetics
JF - American journal of human genetics
IS - 3
ER -