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

  • Background: 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 - LRRTM1 (2p), LRRTM3 (10q), LRRN1 (3p) and LRRN3 (7q) - in order to identify common genetic risk factors underlying ASDs. Methods: 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. Results: Significant results were found for LRRN3 and LRRTM3 (P < 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 LRRTM3. Conclusions: Overall, our findings implicate the neuronal leucine-rich genes LRRN3 and LRRTM3 in ASD susceptibility.
Author:Inês Sousa, Taane Gregrory Clark, Richard Holt, Alistair T. Pagnamenta, Erik J. Mulder, Ruud B. Minderaa, Anthony J. Bailey, Agatino BattagliaORCiDGND, Sabine M. Klauck, Fritz PoustkaGND, Anthony P. Monaco
Pubmed Id:https://pubmed.ncbi.nlm.nih.gov/20678249
Parent Title (English):Molecular autism, 1.2010
Publisher:BioMed Central
Place of publication:London
Document Type:Article
Date of Publication (online):2010/04/27
Date of first Publication:2010/03/25
Publishing Institution:Universitätsbibliothek Johann Christian Senckenberg
Creating Corporation:International Molecular Genetic Study of Autism Consortium (IMGSAC)
Release Date:2010/04/27
Issue:Art. 7
Page Number:14
First Page:1
Last Page:14
© 2010 Sousa et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Institutes:Medizin / Medizin
Dewey Decimal Classification:6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit
Licence (German):License LogoCreative Commons - Namensnennung 2.0