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

Arch Gen Psychiatry. 2009 Apr;66(4):408-16. doi: 10.1001/archgenpsychiatry.2009.6.


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 obsessive-compulsive 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.

Publication types

  • Research Support, N.I.H., Intramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Alleles
  • Brain / metabolism
  • Case-Control Studies
  • Cell Line
  • Excitatory Amino Acid Transporter 3 / genetics*
  • Female
  • Gene Expression / genetics
  • Genes, Reporter / genetics
  • Genetic Predisposition to Disease / genetics
  • Genotype
  • Haplotypes*
  • Humans
  • Linkage Disequilibrium
  • Male
  • Middle Aged
  • Obsessive-Compulsive Disorder / diagnosis
  • Obsessive-Compulsive Disorder / genetics*
  • Phenotype
  • Polymorphism, Single Nucleotide / genetics
  • Quantitative Trait Loci / genetics*
  • Reverse Transcriptase Polymerase Chain Reaction
  • Young Adult


  • Excitatory Amino Acid Transporter 3