Replication study supports evidence for linkage to 9p24 in obsessive-compulsive disorder.
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 ( alpha =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.
Willour
Virginia L
VL
Department of Psychiatry and Behavioral Sciences, School of Medicine, Bloomberg School of Public Health, The Johns Hopkins University, Baltimore, MD 21287, USA. willour@jhmi.edu
Yao Shugart
Yin
Y
Samuels
Jack
J
Grados
Marco
M
Cullen
Bernadette
B
Bienvenu
O Joseph
OJ
Wang
Ying
Y
Liang
Kung-Yee
KY
Valle
David
D
Hoehn-Saric
Rudolf
R
Riddle
Mark
M
Nestadt
Gerald
G
D002874:Chromosome Mapping; D002899:Chromosomes, Human, Pair 9; D008040:Genetic Linkage; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008126:Lod Score; D018895:Microsatellite Repeats; D009771:Obsessive-Compulsive Disorder / Q000235:genetics*; D010375:Pedigree; D010641:Phenotype; D015398:Signal Transduction
D005819:Genetic Markers