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 language | English |
|---|---|
| Pages (from-to) | 408-416 |
| Number of pages | 9 |
| Journal | Archives of General Psychiatry |
| Volume | 66 |
| Issue number | 4 |
| DOIs | |
| State | Published - Apr 1 2009 |
| Externally published | Yes |
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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 journal › Article
}
TY - JOUR
T1 - A haplotype containing quantitative trait loci for SLC1A1 gene expression and its association with obsessive-compulsive disorder
AU - Wendland, Jens R.
AU - Moya, Pablo R.
AU - Timpano, Kiara R
AU - Anavitarte, Adriana P.
AU - Kruse, Matthew R.
AU - Wheaton, Michael G.
AU - Ren-Patterson, Renee F.
AU - Murphy, Dennis L.
PY - 2009/4/1
Y1 - 2009/4/1
N2 - 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.
AB - 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.
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U2 - 10.1001/archgenpsychiatry.2009.6
DO - 10.1001/archgenpsychiatry.2009.6
M3 - Article
VL - 66
SP - 408
EP - 416
JO - JAMA Psychiatry
JF - JAMA Psychiatry
SN - 2168-622X
IS - 4
ER -