A family-based association study of the glutamate transporter gene SLC1A1 in obsessive-compulsive disorder in 378 families.
SLC1A encodes the neuronal and epithelial glutamate transporter and was previously tested as a candidate for obsessive-compulsive disorder (OCD) by several research groups. Recently, three independent research groups reported significant association findings between OCD and several genetic variants in SLC1A1. This study reports the results from a family-based association study, which examined the association between 13 single nucleotide polymorphisms (SNPs) within or in proximity to the SLC1A1 gene. Although we did not replicate association findings for those significant SNPs reported by previous studies, our study indicated a strong association signal with the SNP RS301443 (P-value = 0.000067; Bonferroni corrected P-value = 0.0167) under a dominant model, with an estimated odds ratio of 3.5 (confidence interval: 2.66-4.50). Further, we conducted single SNP analysis after stratifying the full data set by the gender status of affected in each family. The P-value for RS301443 in families with the male affected was 0.00027, and the P-value in families with female affected was 0.076. The fact that we identified a signal which was not previously reported by the other research groups may be due to differences in study designs and sample ascertainment. However, it is also possible that this significant SNP may be part of a regulator for SLC1A1, given that it is roughly 7.5 kb away from the boundary of the SLC1A1 gene. However, this potential finding needs to be validated biologically. Further functional studies in this region are planned by this research group.
Shugart
Y Y
YY
Department of Epidemiology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland 21044, USA. yyao@jhsph.edu
Wang
Y
Y
Samuels
J F
JF
Grados
M A
MA
Greenberg
B D
BD
Knowles
J A
JA
McCracken
J T
JT
Rauch
S L
SL
Murphy
D L
DL
Rasmussen
S A
SA
Cullen
B
B
Hoehn-Saric
R
R
Pinto
A
A
Fyer
A J
AJ
Piacentini
J
J
Pauls
D L
DL
Bienvenu
O J
OJ
Riddle
M A
MA
Liang
K Y
KY
Nestadt
G
G
D000293:Adolescent; D017668:Age of Onset; D002648:Child; D050580:Excitatory Amino Acid Transporter 3 / Q000235:genetics*; D005190:Family; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008297:Male; D009679:Nuclear Family; D009771:Obsessive-Compulsive Disorder / Q000235:genetics*; D010375:Pedigree; D020641:Polymorphism, Single Nucleotide; D055815:Young Adult
D050580:Excitatory Amino Acid Transporter 3; C493400:SLC1A1 protein, human