Abstract
SLC1A1 encodes a neuronal glutamate transporter and is a promising candidate gene for obsessiveβcompulsive 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 7.5βkb downstream of the gene [Shugart et al. (2009); Am J Med Genet Part B 150B:886β892]. 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 9βkb upstream to 84βkb downstream of the gene at average spacing of 1.7βkb per SNP, and conducted familyβbased 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 8.8βkb upstream of the gene, was associated with OCD in all families (Pβ=β0.003) and in families with male affecteds (Pβ=β0.002). A threeβSNP haplotype (rs4740788βrs10491734βrs10491733) was associated with OCD in the total sample (Pβ=β0.00015) and in families with male affecteds (Pβ=β0.0007). 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. Β© 2011 WileyβLiss, Inc.