Family-Based Association Testing of OCD-associated SNPs of SLC1A1 in an autism sample.
Reports identified the neuronal glutamate transporter gene, SLC1A1 (OMIM 133550, chromosome 9p24), as a positional and functional candidate gene for obsessive-compulsive disorder (OCD). The presence of obsessions and compulsions similar to OCD in autism, the identification of this region in a genome-wide linkage analysis of individuals with autism spectrum disorders (ASDs), and the hypothesized role of glutamate in ASDs make SLC1A1 a candidate gene for ASD as well. To test for association between SLC1A1 and autism, we typed three single nucleotide polymorphisms (SNPs, rs301430, rs301979, rs301434) previously associated with OCD in 86 strictly defined trios with autism. Family-Based Association Tests (FBAT) with additive and recessive models were used to check for association. Additionally, an rs301430-rs301979 haplotype identified for OCD was investigated. FBAT revealed nominally significant association between autism and one SNP under a recessive model. The G allele of rs301979 was undertransmitted (equivalent to overtransmission of the C allele under a dominant model) to individuals with autism (Z=-2.47, P=0.01). The G allele was also undertransmitted in the T-G haplotype under the recessive model (Z=-2.41, P=0.02). Both findings were also observed in the male-only sample. However, they did not withstand correction for multiple comparisons.
Brune
Camille W
CW
Institute for Juvenile Research, Department of Psychiatry, University of Illinois-Chicago, Chicago, Illinois 60608, USA.
Kim
Soo-Jeong
SJ
Hanna
Gregory L
GL
Courchesne
Eric
E
Lord
Catherine
C
Leventhal
Bennett L
BL
Cook
Edwin H
EH
D001321:Autistic Disorder / Q000453:epidemiology*; D002648:Child; D002675:Child, Preschool; D050580:Excitatory Amino Acid Transporter 3 / Q000235:genetics*; D005260:Female; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D008297:Male; D009771:Obsessive-Compulsive Disorder / Q000453:epidemiology* / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*
D050580:Excitatory Amino Acid Transporter 3; C493400:SLC1A1 protein, human