The DLX1and DLX2 genes and susceptibility to autism spectrum disorders
- 27 August 2008
- journal article
- Published by Springer Nature in European Journal of Human Genetics
- Vol. 17 (2), 228-235
- https://doi.org/10.1038/ejhg.2008.148
Abstract
An imbalance between excitation and inhibition in the cerebral cortex has been suggested as a possible etiology of autism. The DLX genes encode homeodomain-containing transcription factors controlling the generation of GABAergic cortical interneurons. The DLX1 and DLX2 genes lie head-to-head in 2q32, a region associated with autism susceptibility. We investigated 6 Tag SNPs within the DLX1/2 genes in two cohorts of multiplex (MPX) and one of simplex (SPX) families for association with autism. Family-based association tests showed strong association with five of the SNPs. The common alleles of rs743605 and rs4519482 were significantly associated with autism (PPcor=0.0046). Findings in a second sample of 169 MPX families not only confirmed the association at rs4519482 (P=0.034) but also showed strong allelic association of the common alleles at rs788172, rs788173 and rs813720 (Pcor=0.0003–0.04). In the combined MPX families, the common alleles were all significantly associated with autism (Pcor=0.0005–0.016). The GGGTG haplotype was over transmitted in the two MPX cohorts and the combined samples [PcorPcor=0.00007 for the combined MPX families, Odds Ratio: 1.75 (95% CI: 1.33–2.30)]. Further testing in 306 SPX families replicated the association at rs4519482 (P=0.033) and the over transmission of the haplotype GGGTG (P=0.012) although P-values were not significant after correction for multiple testing. The findings support the presence of two functional polymorphisms, one in or near each of the DLX genes that increase susceptibility to, or cause, autism in MPX families where there is a greater genetic component for these conditions.Keywords
This publication has 51 references indexed in Scilit:
- The Relationship Between Restrictive and Repetitive Behaviors in Individuals with Autism and Obsessive Compulsive Symptoms in ParentsChild Psychiatry and Human Development, 2005
- A Comparison of Case‐Control and Family‐Based Association Methods: The Example of Sickle‐Cell and MalariaAnnals of Human Genetics, 2005
- The vertebrate ortholog of Aristaless is regulated by Dlx genes in the developing forebrainJournal of Comparative Neurology, 2005
- Analysis of the autism chromosome 2 linkage region: GAD1 and other candidate genesNeuroscience Letters, 2004
- Haploview: analysis and visualization of LD and haplotype mapsBioinformatics, 2004
- No association between single nucleotide polymorphisms in DLX6 and piccolo genes at 7q21-q22 and autismAmerican Journal of Medical Genetics, 2003
- A Genomewide Screen for Autism: Strong Evidence for Linkage to Chromosomes 2q, 7q, and 16pAmerican Journal of Human Genetics, 2001
- Towards a Cognitive Phenotype for Autism: Increased Prevalence of Executive Dysfunction and Superior Spatial Span amongst Siblings of Children with AutismJournal of Child Psychology and Psychiatry, 1999
- Neuropsychiatric Assessmenit of Children with Autism: A Population‐Based StudyDevelopmental Medicine and Child Neurology, 1991
- Neurobiological Findings In 20 Relatively Gifted Children With Kanner‐Type Autism Or Asperger SyndromeDevelopmental Medicine and Child Neurology, 1987