TY  - JOUR
T1  - A haplotype containing quantitative trait loci for slc1a1 gene expression and its association with obsessive-compulsive disorder
AU  - Wendland JR, Moya PR, Timpano KR, et al
Y1  - 2009/04/01
N1  - 10.1001/archgenpsychiatry.2009.6
JO  - Archives of General Psychiatry
SP  - 408
EP  - 416
VL  - 66
IS  - 4
N2  - 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.
SN  - 0003-990X
M3  - doi: 10.1001/archgenpsychiatry.2009.6
UR  - http://dx.doi.org/10.1001/archgenpsychiatry.2009.6
ER  -