Association of the SLC1A1 glutamate transporter gene and obsessive-compulsive disorder.
BACKGROUND
Obsessive-Compulsive Disorder (OCD) is a debilitating illness with putative glutamatergic abnormalities. Two separate proximal haplotypes in the glutamate transporter gene, SLC1A1, were recently reported to be associated with OCD among males, but replication is required.


OBJECTIVE
This study examines SLC1A1 as a candidate gene for OCD and explores gender influences. It was hypothesized that a significant association between SLC1A1 and OCD would be replicated in an independent sample of males but not females.


METHODS
Family-based association candidate gene study.


METHODS
Participants were recruited from tertiary care OCD specialty clinics.


METHODS
OCD probands and their first degree relatives.


METHODS
Association of OCD with genotypes of single nucleotide polymorphism (SNP) markers and related haplotypes.


RESULTS
Association between OCD and the three-marker haplotype rs12682807/ rs2072657/ rs301430, with overtransmission of A/T/T, was observed in both genders combined (global P = 0.0015) and in males (global P = 0.0031). Single-marker associations with OCD in the region (rs3780412 and rs2228622) demonstrated modest significance (permuted P = 0.045).


CONCLUSIONS
This study identifies a significant association between the SLC1A1 glutamate transporter gene and OCD in a haplotype overlapping with that recently reported.
Stewart
S Evelyn
SE
Psychiatric Neurodevelopmental and Genetics Unit, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts 02114, USA.
Fagerness
Jesen A
JA
Platko
Jill
J
Smoller
Jordan W
JW
Scharf
Jeremiah M
JM
Illmann
Cornelia
C
Jenike
Eric
E
Chabane
Nadia
N
Leboyer
Marion
M
Delorme
Richard
R
Jenike
Michael A
MA
Pauls
David L
DL
D000293:Adolescent; D017677:Age Distribution; D017668:Age of Onset; 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; D009771:Obsessive-Compulsive Disorder / Q000175:diagnosis / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D017678:Sex Distribution
D050580:Excitatory Amino Acid Transporter 3; C493400:SLC1A1 protein, human