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Arch Gen Psychiatry. 2006 Jul;63(7):778-85.

Association testing of the positional and functional candidate gene SLC1A1/EAAC1 in early-onset obsessive-compulsive disorder.

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  • 1Department of Human Genetics, University of Chicago, Chicago, IL, USA.

Abstract

CONTEXT:

The first 2 independent linkage studies for obsessive-compulsive disorder (OCD) identified a region on 9p24 with suggestive evidence for linkage. The glutamate transporter gene solute carrier family 1, member 1 (SLC1A1) is a promising functional candidate in this region because altered glutamatergic concentrations have been found in the striatum and anterior cingulate in neuroimaging studies of pediatric OCD.

OBJECTIVE:

To determine whether genotypes at polymorphisms in the SLC1A1 gene region are associated with early-onset OCD.

DESIGN:

Family-based analysis of association using the transmission disequilibrium test, confirmed using the family-based association test.

SETTING:

Anxiety disorders program in an academic medical center.

PARTICIPANTS:

Seventy-one probands with DSM-III-R or DSM-IV OCD and their parents.

METHODS:

Nine single nucleotide polymorphisms spaced throughout the SLC1A1 gene region were genotyped.

RESULTS:

Significant association was detected at rs3780412 (P = .04) and rs301430 (P = .03), 2 common adjacent single nucleotide polymorphisms in the 3' region of SLC1A1. Analysis by sex revealed that association at rs3780412 was limited to male probands (P = .002). Significant association was also detected for the T/C haplotype at rs301430-rs301979 (P = .03), the only haplotype block identified among the 9 single nucleotide polymorphisms. Analysis by sex also revealed that the haplotype association was limited to male probands (P = .003). A deletion in the 3' flanking region of SLC1A1 was also detected that imperfectly segregated with OCD in a large, multigenerational family with multiple affected individuals.

CONCLUSIONS:

The 3' region of SLC1A1 may contain a susceptibility allele for early-onset OCD, with differential effects in males and females. The results also provide further support for the involvement of a glutamatergic dysfunction in the pathogenesis of early-onset OCD.

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PMID:
16818867
[PubMed - indexed for MEDLINE]
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