A haplotype containing quantitative trait loci for SLC1A1 gene expression and its association with obsessive-compulsive disorder.
paper
Cited
Public
- Authors
- 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
- Year
- 2009
- Journal
- Archives of general psychiatry
- PMID
- 19349310
- DOI
- 10.1001/archgenpsychiatry.2009.6
- PMCID
- PMC2775716
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.
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| Name | Type |
|---|---|
| 3-marker haplotype local | variant |
| 5β² exonuclease assay local | drug |
| Acquisition subscale local | phenotype |
| Adult OCD probands local | cohort |
| alcohol abuse | phenotype |
| anxiety | phenotype |
| Arnold et al study local | cohort |
| bipolar disorder | phenotype |
| brain | anatomy |
| case-control sample | cohort |
| CEPH database local | cohort |
| clinical OCD sample local | cohort |
| Clutter subscale local | phenotype |
| Control Cohort 1 local | cohort |
| Control Cohort 2 local | cohort |
| Control Cohort 3 local | cohort |
| controls | cohort |
| Dickel et al study local | cohort |
| Difficulty discarding subscale local | phenotype |
| disease | phenotype |
| DNA | drug |
| dorsolateral prefrontal cortex | anatomy |
| Dual Luciferase Reporter Assay System | drug |
| early-onset obsessive-compulsive disorder local | phenotype |
| family-based association studies local | cohort |
| gene expression | phenotype |
| GSE1485 local | cohort |
| H2 local | variant |
| H4 local | variant |
| HapMap CEU founders local | cohort |
| hoarding | phenotype |
| Hoarding local | other |
| hoarding factor local | phenotype |
| Hoarding factor local | other |
| Hoarding phenotype local | phenotype |
| lymphoblastoid cell lines | cohort |
| major depressive disorder | phenotype |
| mood disorders | phenotype |
| normal | phenotype |
| obsessive-compulsive disorder | phenotype |
| OCD | phenotype |
| OCD controls local | cohort |
| OCD hoarding subphenotype local | phenotype |
| OCD probands | cohort |
| oligo-dT primers local | drug |
| Oragene disc local | drug |
| pCR2.1 local | drug |
| PerfeCta qPCR FastMix local | drug |
| PGK1 | gene |
| pGL3 reporter vector local | drug |
| population stratification | phenotype |
| Postmortem brain cohort local | cohort |
| probands | cohort |
| proband sample local | cohort |
| risk allele | cohort |
| rs301430 local | variant |
| rs3087879 local | variant |
| rs3780412 local | variant |
| rs3933331 local | variant |
| rs7858819 local | variant |
| saliva | drug |
| Saving InventoryβRevised (SIR) local | phenotype |
| Saving Inventory-Revised total score local | phenotype |
| schizophrenia | phenotype |
| screened controls | cohort |
| SIR local | phenotype |
| SIR-assessed hoarding local | phenotype |
| SLC1A1 | gene |
| SLC1A1 eQTL SNPs local | variant |
| SLC1A1 expression local | phenotype |
| SLC1A1 family-associated SNPs local | variant |
| SLC1A1 gene expression local | phenotype |
| SLC6A4 | gene |
| SNP | cohort |
| Stanley cohort local | cohort |
| Stanley Medical Research Institute data bank local | cohort |
| Stewart et al study local | cohort |
| substance abuse | phenotype |
| three-generational families local | cohort |
| tics | phenotype |
| Transcriptor First Strand cDNA Synthesis kit local | drug |
| Universal Probe Library probe No. 9 local | drug |
| unscreened controls local | cohort |
| uracil-N-glycosylase | drug |
| white participants | cohort |
| whole blood | anatomy |
| Y-BOCS hoarding symptom dimension local | phenotype |
| Y-BOCS score local | phenotype |
| Y-BOCS symptom checklist local | phenotype |
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