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.
Key Words
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Article info
Publication history
Published online: May 28, 2012
Accepted:
March 31,
2012
Received in revised form:
March 20,
2012
Received:
August 4,
2011
Identification
Copyright
© 2012 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.
