Comprehensive family-based association study of the glutamate transporter gene SLC1A1 in obsessive-compulsive disorder
Open accessAbstract
SLC1A1 encodes a neuronal glutamate transporter and is a promising candidate gene for obsessive‐compulsive disorder (OCD). Several independent research groups have reported significant associations between OCD and single nucleotide polymorphisms (SNPs) in this gene. Previously, we evaluated 13 SNPs in, or near, SLC1A1 and reported a strong association signal with rs301443, a SNP 7.5 kb downstream of the gene [Shugart et al. (2009); Am J Med Genet Part B 150B:886–892]. The aims of the current study were first, to further investigate this finding by saturating the region around rs301443; and second, to explore the entire gene more thoroughly with a dense panel of SNP markers. We genotyped an additional 111 SNPs in or near SLC1A1, covering from 9 kb upstream to 84 kb downstream of the gene at average spacing of 1.7 kb per SNP, and conducted family‐based association analyses in 1,576 participants in 377 families. We found that none of the surrounding markers were in linkage disequilibrium with rs301443, nor were any associated with OCD. We also found that SNP rs4740788, located about 8.8 kb upstream of the gene, was associated with OCD in all families (P = 0.003) and in families with male affecteds (P = 0.002). A three‐SNP haplotype (rs4740788–rs10491734–rs10491733) was associated with OCD in the total sample (P = 0.00015) and in families with male affecteds (P = 0.0007). Although of nominal statistical significance considering the number of comparisons, these findings provide further support for the involvement of SLC1A1 in the pathogenesis of OCD. © 2011 Wiley‐Liss, Inc.
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SLC1A1 is one of the more consistently replicated genetic findings in OCD.
“One of the more consistently replicated genetic findings in OCD is an association with the neuronal glutamate transporter SLC1A1 (protein: EAAT3 or EAAC1) 18–24”
From DISSECTING OCD CIRCUITS: FROM ANIMAL MODELS TO TARGETED TREATMENTS: Review: Dissecting OCD Circuits: Animals to Treatments (2015) · cites this paper as [24]
rs4740788 was associated with OCD in all families and in families with affected males.
“These authors, however, found that rs4740788 was associated with OCD in all families and in families with affected males.”
From The neurobiological link between OCD and ADHD (2014) · cites this paper as Samuels et al. 2011
A three-SNP haplotype (rs4740788-rs10491734-rs10491733) was associated with OCD in the total sample.
“A three-SNP haplotype (rs4740788–rs10491734–rs10491733) was associated with OCD in the total sample (Samuels et al. 2011).”
From The neurobiological link between OCD and ADHD (2014) · cites this paper as Samuels et al. 2011
None of the surrounding markers were in linkage disequilibrium with rs301443 nor were any associated with OCD.
“None of the surrounding markers were in linkage disequilibrium with rs301443 (SNP 7.5 kb downstream of the SLC1A1 gene) nor were any associated with OCD.”
From The neurobiological link between OCD and ADHD (2014) · cites this paper as Samuels et al. 2011
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- Authors
- Samuels, J., Wang, Y., Riddle, M. A., Greenberg, B. D., Fyer, A. J., McCracken, J. T., Rauch, S. L., Murphy, D. L., Grados, M. A., Knowles, J. A., Piacentini, J., Cullen, B., Bienvenu, O. J., Rasmussen, S. A., Geller, D., Pauls, D. L., Liang, K., Shugart, Y. Y., & Nestadt, G.
- Affiliations
- Johns Hopkins University (US)
- Butler Hospital (US)
- New York State Psychiatric Institute (US)
- University of California, Los Angeles (US)
- Harvard University (US)
- National Institutes of Health (US)
- University of Southern California (US)
- Corresponding author
- Samuels, Jack
- ORCID
- Venue
- American Journal of Medical Genetics Part B: Neuropsychiatric Genetics
- Publisher
- Wiley
- Published
- 2011-03-28
- Volume
- 156
- Issue
- 4
- Pages
- 472-477
- ISSN
- 1552-4841 (ISSN-L)
- 1552-485X
- PMC
- PMC3082623
- OpenAlex
- W2078966869
- Cited by
- 89
- References
- 39
- Citations by year
- 2026: 1 · 2025: 2 · 2024: 4 · 2023: 4 · 2022: 2 · 2021: 4 · 2020: 6 · 2019: 8 · 2018: 7 · 2017: 7 · 2016: 5 · 2015: 6 · 2014: 11 · 2013: 9 · 2012: 8
- FWCI
- 11.05
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- American Journal of Medical Genetics Part B Neuropsychiatric Genetics (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Yale University
- Brown University
- Johns Hopkins University
- National Institute of Mental Health (R01MH050214, R01MH071507, R01 MH 50214)
- National Center for Research Resources (RR 000 52, M01RR000052)
- Topics
- Social Sciences › Psychology › Clinical Psychology › Obsessive-Compulsive Spectrum Disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Keywords
- SLC1A1, glutamate transporters, obsessive-compulsive disorder, family-based association, single nucleotide polymorphisms, haplotype association, linkage disequilibrium, candidate genes
- MeSH terms
- Family, Genotype, Haplotypes, Humans, Male, Obsessive-Compulsive Disorder, Genetic Predisposition to Disease, Polymorphism, Single Nucleotide, Excitatory Amino Acid Transporter 3
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