title: Comprehensive family-based association study of the glutamate transporter gene SLC1A1 in obsessive-compulsive disorder.
abstract: 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.
authors: Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA. jacks@jhmi.edu
authors: Jack
authors: J
authors: Samuels
authors: Ying
authors: Y
authors: Wang
authors: Mark A
authors: MA
authors: Riddle
authors: Benjamin D
authors: BD
authors: Greenberg
authors: Abby J
authors: AJ
authors: Fyer
authors: James T
authors: JT
authors: McCracken
authors: Scott L
authors: SL
authors: Rauch
authors: Dennis L
authors: DL
authors: Murphy
authors: Marco A
authors: MA
authors: Grados
authors: James A
authors: JA
authors: Knowles
authors: John
authors: J
authors: Piacentini
authors: Bernadette
authors: B
authors: Cullen
authors: O Joseph
authors: OJ
authors: Bienvenu
authors: Steven A
authors: SA
authors: Rasmussen
authors: Daniel
authors: D
authors: Geller
authors: David L
authors: DL
authors: Pauls
authors: Kung-Yee
authors: KY
authors: Liang
authors: Yin Y
authors: YY
authors: Shugart
authors: Gerald
authors: G
authors: Nestadt
mesh_terms: D050580:Excitatory Amino Acid Transporter 3 / Q000235:genetics*; D005190:Family; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D008297:Male; D009771:Obsessive-Compulsive Disorder / Q000209:etiology* / Q000235:genetics; D020641:Polymorphism, Single Nucleotide
chemical_list: D050580:Excitatory Amino Acid Transporter 3; C493400:SLC1A1 protein, human