Evidence for a susceptibility locus on chromosome 10p15 in early-onset obsessive-compulsive disorder.
BACKGROUND
The goal of this study was to identify chromosomal regions likely to contain susceptibility loci for obsessive-compulsive disorder (OCD).


METHODS
We conducted a genome-wide linkage scan, with average marker spacing less than 10 centimorgans (cM), in 121 subjects from 26 families ascertained through probands with early-onset OCD. Best estimate lifetime psychiatric diagnoses were based on semistructured interviews and all other available sources of information. Parametric and nonparametric linkage analyses were conducted with GENEHUNTER+ and Allegro. Family-based association analyses were done using 35 single nucleotide polymorphisms (SNPs) in the 10p15 region.


RESULTS
The maximum nonparametric log of odds (NLOD) score was 2.43 on chromosome 10p15 at position 4.37. When data from our first genome scan were added to data from this scan, the maximum NLOD score in the 10p15 region was 1.79. Association was detected on 10p15 with three adjacent SNPs, including the amino acid variant rs2271275 in the 3' region of adenosine deaminase acting on RNA 3 (ADAR3) (p < .05).


CONCLUSIONS
The results provide suggestive evidence for linkage on chromosome 10p15. Evidence for association in the linkage region was found with three markers in the 3' end of ADAR3. Limitations include the lack of significant linkage and association findings when corrected for multiple testing.
Hanna
Gregory L
GL
Department of Psychiatry, University of Michigan, Ann Arbor, Michigan 48105, USA. ghanna@umich.edu
Veenstra-Vanderweele
Jeremy
J
Cox
Nancy J
NJ
Van Etten
Michelle
M
Fischer
Daniel J
DJ
Himle
Joseph A
JA
Bivens
Nancy Chiu
NC
Wu
Xiaolin
X
Roe
Cheryl A
CA
Hennessy
Kathleen A
KA
Dickel
Diane E
DE
Leventhal
Bennett L
BL
Cook
Edwin H
EH
D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D002879:Chromosomes, Human, Pair 10 / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006801:Humans; D015810:Linkage Disequilibrium; D008297:Male; D008875:Middle Aged; D009771:Obsessive-Compulsive Disorder / Q000235:genetics*; D010375:Pedigree; D018709:Statistics, Nonparametric