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Biol Psychiatry. 2012 Oct 15;72(8):629-36. doi: 10.1016/j.biopsych.2012.03.037. Epub 2012 May 25.

Genome-wide linkage analysis of obsessive-compulsive disorder implicates chromosome 1p36.

Author information

  • 1Department of Psychiatry, University of California, San Francisco, San Francisco, CA 94143-0984, USA. cmathews@lppi.ucsf.edu

Abstract

BACKGROUND:

Obsessive-compulsive disorder (OCD) has a complex etiology involving both genetic and environmental factors. However, the genetic causes of OCD are largely unknown, despite the identification of several promising candidate genes and linkage regions.

METHODS:

Our objective was to conduct genetic linkage studies of the type of OCD thought to have the strongest genetic etiology (i.e., childhood-onset OCD), in 33 Caucasian families with ≥2 childhood-onset OCD-affected individuals from the United States (n = 245 individuals with genotype data). Parametric and nonparametric genome-wide linkage analyses were conducted with Morgan and Merlin in these families using a selected panel of single nucleotide repeat polymorphisms from the Illumina 610-Quad Bead Chip. The initial analyses were followed by fine-mapping analyses in genomic regions with initial heterogeneity logarithm of odds (HLOD) scores of ≥2.0.

RESULTS:

We identified five areas of interest (HLOD score ≥2) on chromosomes 1p36, 2p14, 5q13, 6p25, and 10p13. The strongest result was on chromosome 1p36.33-p36.32 (HLOD = 3.77, suggestive evidence for linkage after fine mapping). At this location, several of the families showed haplotypes co-segregating with OCD.

CONCLUSIONS:

The results of this study represent the strongest linkage finding for OCD in a primary analysis to date and suggest that chromosome 1p36, and possibly several other genomic regions, may harbor susceptibility loci for OCD. Multiple brain-expressed genes lie under the primary linkage peak (approximately 4 megabases in size). Follow-up studies, including replication in additional samples and targeted sequencing of the areas of interest, are needed to confirm these findings and to identify specific OCD risk variants.

Copyright © 2012 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

PMID:
22633946
[PubMed - indexed for MEDLINE]
PMCID:
PMC3437244
Free PMC Article

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