Polymorphisms in leucine-rich repeat genes are associated with autism spectrum disorder susceptibility in populations of European ancestry

• Main Authors: Sousa Inês, Clark Taane G, Holt Richard, Pagnamenta Alistair T, Mulder Erik J, Minderaa Ruud B, Bailey Anthony J, Battaglia Agatino, Klauck Sabine M, Poustka Fritz, Monaco Anthony P
• Format: Article
• Language: English
• Published: BMC 2010-03-01
• Series: Molecular Autism
• Online Access: http://www.molecularautism.com/content/1/1/7

<p>Abstract</p> <p>Background</p> <p>Autism spectrum disorders (ASDs) are a group of highly heritable neurodevelopmental disorders which are characteristically comprised of impairments in social interaction, communication and restricted interests/behaviours. Several cell adhesion transmembrane leucine-rich repeat (LRR) proteins are highly expressed in the nervous system and are thought to be key regulators of its development. Here we present an association study analysing the roles of four promising candidate genes - <it>LRRTM1 </it>(2p), <it>LRRTM3 </it>(10q), <it>LRRN1 </it>(3p) and <it>LRRN3 </it>(7q) - in order to identify common genetic risk factors underlying ASDs.</p> <p>Methods</p> <p>In order to gain a better understanding of how the genetic variation within these four gene regions may influence susceptibility to ASDs, a family-based association study was undertaken in 661 families of European ancestry selected from four different ASD cohorts. In addition, a case-control study was undertaken across the four LRR genes, using logistic regression in probands with ASD of each population against 295 ECACC controls.</p> <p>Results</p> <p>Significant results were found for <it>LRRN3 </it>and <it>LRRTM3 </it>(<it>P </it>< 0.005), using both single locus and haplotype approaches. These results were further supported by a case-control analysis, which also highlighted additional SNPs in <it>LRRTM3</it>.</p> <p>Conclusions</p> <p>Overall, our findings implicate the neuronal leucine-rich genes <it>LRRN3 </it>and <it>LRRTM3 </it>in ASD susceptibility.</p>