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Glutamate TransporterGene SLC1A1Associated WithObsessive-compulsiveDisorder Paul ArnoldTricia SicardEliza Burroughs2006 год

Glutamate Transporter Gene SLC1A1 Associated With Obsessive-compulsive Disorder
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Аннотация:

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.SLC1A1represents 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 inSLC1A1are 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 withDSM-IVOCD recruited from consecutive referrals and their first-degree relatives (476 individuals in total).

Intervention

Nine single nucleotide polymorphisms spanningSLC1A1were genotyped. Single-locus and haplotype analyses were performed using the Family-Based Association Test and the Transmission Disequilibrium Test. Traits examined includedDSM-IVOCD 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 (χ2 = 12.04;P = .006) and rs301435 (χ2 = 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 (χ2 = 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 inSLC1A1is 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.
Год издания: 2006
Авторы: Paul Arnold, Tricia Sicard, Eliza Burroughs, Margaret A. Richter, James L. Kennedy
Издательство: American Medical Association
Источник: Archives of General Psychiatry
Ключевые слова: Obsessive-Compulsive Spectrum Disorders, Autism Spectrum Disorder Research, Neurotransmitter Receptor Influence on Behavior
Другие ссылки: Archives of General Psychiatry (HTML)
PubMed (HTML)