A haplotype containing quantitative trait loci for SLC1A1 gene expression and its association with obsessive-compulsive disorder

Jens R. Wendland, Pablo R. Moya, Kiara R Timpano, Adriana P. Anavitarte, Matthew R. Kruse, Michael G. Wheaton, Renee F. Ren-Patterson, Dennis L. Murphy

Research output: Contribution to journalArticle

89 Citations (Scopus)

Abstract

Context: Recent evidence from linkage analyses and follow-up candidate gene studies supports the involvement of SLC1A1, which encodes the neuronal glutamate transporter, in the development of obsessivecompulsive disorder (OCD). Objectives: To determine the role of genetic variation of SLC1A1 in OCD in a large case-control study and to better understand how SLC1A1 variation affects functionality. Design: A case-control study. Setting: Publicly accessible SLC1A1 expression and genotype data. Patients: Three hundred twenty-five OCD probands and 662 ethnically and sex-matched controls. Interventions: Probands were assessed with the Structured Clinical Interview for DSM-IV, the Yale-Brown Obsessive Compulsive Scale, and the Saving Inventory- Revised. Six single-nucleotide polymorphisms (SNPs) were genotyped. Multiple testing corrections for single-marker and haplotype analyses were performed by permutation. Results: Gene expression of SLC1A1 is heritable in lymphoblastoid cell lines. We identified 3 SNPs in or near SLC1A1 that correlated with gene expression levels, 1 of which had previously been associated with OCD. Two of these SNPs also predicted expression levels in human brain tissue, and 1 SNP was further functional in reporter gene studies. Two haplotypes at 3 SNPs, rs3087879, rs301430, and rs7858819, were significantly associated with OCD after multiple-testing correction and contained 2 SNPs associated with expression levels. In addition, another SNP correlating with SLC1A1 gene expression, rs3933331, was associated with an OCD- hoarding subphenotype as assessed by 2 independent, validated scales. Conclusions: Our case-control data corroborate previous smaller family-based studies that indicated that SLC1A1 is a susceptibility locus for OCD. The expression and genotype database-mining approach we used provides a potentially useful complementary approach to strengthen future candidate gene studies in neuropsychiatric and other disorders.

Original languageEnglish
Pages (from-to)408-416
Number of pages9
JournalArchives of General Psychiatry
Volume66
Issue number4
DOIs
StatePublished - Apr 1 2009
Externally publishedYes

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Quantitative Trait Loci
Obsessive-Compulsive Disorder
Haplotypes
Single Nucleotide Polymorphism
Gene Expression
Case-Control Studies
Genotype
Amino Acid Transport System X-AG
Reporter Genes
Diagnostic and Statistical Manual of Mental Disorders
Genes
Databases
Interviews
Cell Line
Equipment and Supplies
Brain

ASJC Scopus subject areas

  • Psychiatry and Mental health

Cite this

A haplotype containing quantitative trait loci for SLC1A1 gene expression and its association with obsessive-compulsive disorder. / Wendland, Jens R.; Moya, Pablo R.; Timpano, Kiara R; Anavitarte, Adriana P.; Kruse, Matthew R.; Wheaton, Michael G.; Ren-Patterson, Renee F.; Murphy, Dennis L.

In: Archives of General Psychiatry, Vol. 66, No. 4, 01.04.2009, p. 408-416.

Research output: Contribution to journalArticle

Wendland, Jens R. ; Moya, Pablo R. ; Timpano, Kiara R ; Anavitarte, Adriana P. ; Kruse, Matthew R. ; Wheaton, Michael G. ; Ren-Patterson, Renee F. ; Murphy, Dennis L. / A haplotype containing quantitative trait loci for SLC1A1 gene expression and its association with obsessive-compulsive disorder. In: Archives of General Psychiatry. 2009 ; Vol. 66, No. 4. pp. 408-416.
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AU - Anavitarte, Adriana P.

AU - Kruse, Matthew R.

AU - Wheaton, Michael G.

AU - Ren-Patterson, Renee F.

AU - Murphy, Dennis L.

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