@article{205ee7736420427ba99a29ffa75427b5,
title = "Genomewide linkage scan for obsessive-compulsive disorder: Evidence for susceptibility loci on chromosomes 3q, 7p, 1q, 15q, and 6q",
abstract = "Obsessive-compulsive disorder (OCD) is the tenth most disabling medical condition worldwide. Twin and family studies implicate a genetic etiology for this disorder, although specific genes have yet to be identified. Here, we present the first large-scale model-free linkage analysis of both extended and nuclear families using both 'broad' (definite and probable diagnoses) and 'narrow' (definite only) definitions of OCD. We conducted a genome-scan analysis of 219 families collected as part of the OCD Collaborative Genetics Study. Suggestive linkage signals were revealed by multipoint analysis on chromosomes 3q27-28 (P=0.0003), 6q (P=0.003), 7p (P=0.001), 1q (P=0.003), and 15q (P=0.006). Using the 'broad' OCD definition, we observed the strongest evidence for linkage on chromosome 3q27-28. The maximum overall Kong and Cox LOD all score (2.67) occurred at D3S1262 and D3S2398, and simulation based P-values for these two signals were 0.0003 and 0.0004, respectively, although for both signals, the simulation-based genome-wide significance levels were 0.055. Covariate-linkage analyses implicated a possible role of gene(s) on chromosome 1 in increasing the risk for an earlier onset form of OCD. We are currently pursuing fine mapping in the five regions giving suggestive signals, with a particular focus on 3q27-28. Given probable etiologic heterogeneity in OCD, mapping gene(s) involved in the disorder may be enhanced by replication studies, large-scale family-based linkage studies, and the application of novel statistical methods.",
keywords = "Age of onset, Covariate based linkage analysis, Genome-wide scan, Obsessive-compulsive disorder, Simulation",
author = "Shugart, {Y. Y.} and J. Samuels and Willour, {V. L.} 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 Y. Wang and A. Pinto and Fyer, {A. J.} and J. Piacentini and Pauls, {D. L.} and B. Cullen and J. Page and Rasmussen, {S. A.} and Bienvenu, {O. J.} and R. Hoehn-Saric and D. Valle and Liang, {K. Y.} and Riddle, {M. A.} and G. Nestadt",
note = "Funding Information: Genotyping services at CIDR was funded through the National Institutes of Health via The Johns Hopkins University, Contract Number N01-HG-65403. We are grateful to the numerous individuals and families who generously donated their time and resources, and to the Obsessive Compulsive Foundation. We thank David Houseman, MD, Kathleen Merikangas, PhD, Ann Pulver, PhD, and Alec Wilson, PhD, for consultation; and clinicians and coordinators at each site: Providence (Maria Mancebo, PhD, Richard Mars-land, RN, Shirley Yen, PhD); New York (Renee Goodwin, PhD, Joshua Lipsitz, PhD); Baltimore (Laura Eisen, BS; Karan Lamb, PsyD, Tracey Lichner, PhD, Yung-mei Leong, PhD; Krista Vermillion, BA, Ying Wang, MS); Boston (Dan Geller, MD, Anne Chosak, PhD, Michelle Wedig, BS, Evelyn Stewart, MD, Michael Jenike, MD, Beth Gershuny, PhD, Sabine Wilhelm, PhD); Bethesda (Lucy Justement, Diane Kazuba, V Holland LaSalle-Ricci, Theresa B DeGuz-man); Los Angeles (R Lindsey Bergman, PhD, Susanna Chang, PhD, Audra Langley, PhD, Amanda Pearlman, BA). This study is supported by NIMH R01 MH50214 to GN, K23-MH64543 to OJB, and 7K23MH066284 to MAG from the National Institute of Mental Health, and NIH, NCRR, OPD-GCRC RR 00052 from the National Institutes of Health. YYS is, in part, supported by the Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health.",
year = "2006",
month = aug,
day = "16",
doi = "10.1038/sj.mp.4001847",
language = "English (US)",
volume = "11",
pages = "763--770",
journal = "Molecular psychiatry",
issn = "1359-4184",
publisher = "Nature Publishing Group",
number = "8",
}