Functional studies and rare variant screening of SLC1A1/EAAC1 in males with obsessive–compulsive disorder
Open accessAbstract
Several studies have found that the neuronal glutamate transporter gene SLC1A1/EAAC1 is associated with obsessive-compulsive disorder (OCD), with a stronger association in males. Previous studies have primarily focused on common single-nucleotide polymorphisms, rather than rare functional variants that are likely to have larger effects. We screened 184 males with OCD for rare variation in SLC1A1 exons; however, no new coding variation was found. When combined with previous screens, only one SLC1A1 amino acid variant has been detected among the 841 individuals screened, which is less than for other neurotransmitter transporter genes (P=0.0001). We characterized the function of the one SLC1A1 missense variant reported previously in OCD, Thr164Ala, and found that the Ala164 allele leads to decreased Vmax and Km (P<0.0001) in transfected human embryonic kidney cells. Further work will be necessary to understand the impact of this rare SLC1A1/EAAC1 Ala164 variant on neuronal function and circuitry relevant to OCD.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Coding variants in SLC1A1 are very rare and do not clearly segregate with OCD.
“Coding variants are very rare (3/1400 subjects screened) and do not clearly segregate with OCD 26,27.”
From DISSECTING OCD CIRCUITS: FROM ANIMAL MODELS TO TARGETED TREATMENTS: Review: Dissecting OCD Circuits: Animals to Treatments (2015) · cites this paper as [26]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
The citation lists haven’t been fetched yet
References 39 · Cited by 22
Research works printed but not linked: 2
- Hien D, Matzner FJ, First MB, Spitzer RL, Gibbon M, Williams JBW. (1994). Structured Clinical Interview for DSM-IV-Child Edition. New York, NY: Columbia University.
- Spitzer R, Williams J, Gibbon M, First M. (1990). Structured Clinical Interview for DSM-III-R (SCID). Washington, DC: American Psychiatric Press, Inc.
- Authors
- Veenstra-VanderWeele, J., Xu, T., Ruggiero, A. M., Anderson, L. R., Jones, S. T., Himle, J. A., Kennedy, J. L., Richter, M. A., Hanna, G. L., & Arnold, P. D.
- Affiliations
- University of Toronto (CA)
- Centre for Addiction and Mental Health (CA)
- Sunnybrook Health Science Centre (CA)
- Corresponding author
- Veenstra-VanderWeele, Jeremy
- ORCID
- Venue
- Psychiatric Genetics
- Published
- 2012-10
- Volume
- 22
- Issue
- 5
- Pages
- 256-260
- ISSN
- 0955-8829 (ISSN-L)
- PMC
- PMC6486951
- OpenAlex
- W2054944592
- Cited by
- 22
- References
- 39
- Citations by year
- 2024: 3 · 2019: 1 · 2018: 2 · 2017: 3 · 2016: 2 · 2015: 3 · 2014: 3 · 2013: 5
- FWCI
- 4.00
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Psychiatric Genetics (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Vanderbilt University
- National Institute of Mental Health (K08MH081066, MH081066, R01MH058376, MH01065, K20MH001065, MH58376)
- National Center for Research Resources (RR024975, KL2RR024977, TL1RR024978, UL1RR024975)
- Topics
- Social Sciences › Psychology › Clinical Psychology › Obsessive-Compulsive Spectrum Disorders
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
- Keywords
- SLC1A1, EAAC1, glutamate transporters, obsessive-compulsive disorder, rare variants, missense mutations, transporter function, sex differences, genetic association
- MeSH terms
- Adolescent, Adult, Child, Genetic Testing, Humans, Kinetics, Male, Middle Aged, Obsessive-Compulsive Disorder, Sequence Analysis, DNA, Glutamic Acid, Genetic Predisposition to Disease, Polymorphism, Single Nucleotide, Excitatory Amino Acid Transporter 3, Young Adult
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
