Glutamate Transporter Gene SLC1A1 Associated With Obsessive-compulsive Disorder
Bibliographic record
Abstract
CONTEXT: There is strong evidence from family and twin studies that genetic determinants play an important role in the etiology of obsessive-compulsive disorder (OCD). In the only genome scan of OCD to date that we are aware of, suggestive linkage was reported to the chromosomal region 9p24, a finding that was subsequently replicated. This region contains the gene encoding the neuronal glutamate transporter, SLC1A1. SLC1A1 represents an excellent candidate gene for OCD based on evidence from neuroimaging and animal studies that altered glutamatergic neurotransmission is implicated in the pathogenesis of this disorder. OBJECTIVE: To determine whether sequence variants in SLC1A1 are associated with transmission of the OCD trait. DESIGN: A family-based candidate gene association study. SETTING: A specialized anxiety disorders outpatient clinic. PARTICIPANTS: One hundred fifty-seven white probands with DSM-IV OCD recruited from consecutive referrals and their first-degree relatives (476 individuals in total). INTERVENTION: Nine single nucleotide polymorphisms spanning SLC1A1 were genotyped. Single-locus and haplotype analyses were performed using the Family-Based Association Test and the Transmission Disequilibrium Test. Traits examined included DSM-IV OCD diagnosis and highest lifetime symptom severity as measured using the Yale-Brown Obsessive-Compulsive Scale. Correction for multiple comparisons was performed using permutation tests. RESULTS: After correction for multiple comparisons, 2 variants, rs301434 (chi 2 = 12.04; P = .006) and rs301435 (chi 2 = 9.24; P = .03), located within a single haplotype block were found to be associated with transmission of OCD. Furthermore, a specific 2-marker haplotype within this block was significantly associated with OCD (chi 2 = 12.60; P = .005). This haplotype association was statistically significant in transmissions to male but not female offspring. CONCLUSIONS: Although requiring replication in larger samples, these findings provide preliminary evidence that sequence variation in SLC1A1 is associated with susceptibility to OCD, particularly in males. Furthermore, these results provide support for the role of altered glutamatergic neurotransmission in the pathogenesis of OCD.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.002 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.001 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.000 |
| Insufficient payload (model declined to judge) | 0.006 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".