title: Association testing of the positional and functional candidate gene SLC1A1/EAAC1 in early-onset obsessive-compulsive disorder.
abstract: BACKGROUND
  The first 2 independent linkage studies for obsessive-compulsive disorder (OCD) identified a region on 9p24 with suggestive evidence for linkage. The glutamate transporter gene solute carrier family 1, member 1 (SLC1A1) is a promising functional candidate in this region because altered glutamatergic concentrations have been found in the striatum and anterior cingulate in neuroimaging studies of pediatric OCD.
  
  
  OBJECTIVE
  To determine whether genotypes at polymorphisms in the SLC1A1 gene region are associated with early-onset OCD.
  
  
  METHODS
  Family-based analysis of association using the transmission disequilibrium test, confirmed using the family-based association test.
  
  
  METHODS
  Anxiety disorders program in an academic medical center.
  
  
  METHODS
  Seventy-one probands with DSM-III-R or DSM-IV OCD and their parents.
  
  
  METHODS
  Nine single nucleotide polymorphisms spaced throughout the SLC1A1 gene region were genotyped.
  
  
  RESULTS
  Significant association was detected at rs3780412 (P = .04) and rs301430 (P = .03), 2 common adjacent single nucleotide polymorphisms in the 3' region of SLC1A1. Analysis by sex revealed that association at rs3780412 was limited to male probands (P = .002). Significant association was also detected for the T/C haplotype at rs301430-rs301979 (P = .03), the only haplotype block identified among the 9 single nucleotide polymorphisms. Analysis by sex also revealed that the haplotype association was limited to male probands (P = .003). A deletion in the 3' flanking region of SLC1A1 was also detected that imperfectly segregated with OCD in a large, multigenerational family with multiple affected individuals.
  
  
  CONCLUSIONS
  The 3' region of SLC1A1 may contain a susceptibility allele for early-onset OCD, with differential effects in males and females. The results also provide further support for the involvement of a glutamatergic dysfunction in the pathogenesis of early-onset OCD.
authors.affiliation: Department of Human Genetics, University of Chicago, Chicago, IL, USA.
authors.forename: Diane E
authors.initials: DE
authors.lastname: Dickel
authors.forename: Jeremy
authors.initials: J
authors.lastname: Veenstra-VanderWeele
authors.forename: Nancy J
authors.initials: NJ
authors.lastname: Cox
authors.forename: Xiaolin
authors.initials: X
authors.lastname: Wu
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Fischer
authors.forename: Michelle
authors.initials: M
authors.lastname: Van Etten-Lee
authors.forename: Joseph A
authors.initials: JA
authors.lastname: Himle
authors.forename: Bennett L
authors.initials: BL
authors.lastname: Leventhal
authors.forename: Edwin H
authors.initials: EH
authors.lastname: Cook
authors.forename: Gregory L
authors.initials: GL
authors.lastname: Hanna
mesh_terms: D000293:Adolescent; D000328:Adult; D000367:Age Factors; D017668:Age of Onset; D000368:Aged; D002648:Child; D002874:Chromosome Mapping; D050580:Excitatory Amino Acid Transporter 3 / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease / Q000235:genetics; D005838:Genotype; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D015810:Linkage Disequilibrium / Q000235:genetics; D008297:Male; D008875:Middle Aged; D009771:Obsessive-Compulsive Disorder / Q000175:diagnosis / Q000235:genetics*; D010375:Pedigree; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D012737:Sex Factors
chemical_list: D050580:Excitatory Amino Acid Transporter 3; C493400:SLC1A1 protein, human