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Molecular Autism
Published in: Molecular Autism 1/2010

Open Access 01-12-2010 | Research

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

Authors: Inês Sousa, Taane G Clark, Richard Holt, Alistair T Pagnamenta, Erik J Mulder, Ruud B Minderaa, Anthony J Bailey, Agatino Battaglia, Sabine M Klauck, Fritz Poustka, Anthony P Monaco, International Molecular Genetic Study of Autism Consortium (IMGSAC)

Published in: Molecular Autism | Issue 1/2010

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Abstract

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.
Appendix
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Metadata
Title
Polymorphisms in leucine-rich repeat genes are associated with autism spectrum disorder susceptibility in populations of European ancestry
Authors
Inês Sousa
Taane G Clark
Richard Holt
Alistair T Pagnamenta
Erik J Mulder
Ruud B Minderaa
Anthony J Bailey
Agatino Battaglia
Sabine M Klauck
Fritz Poustka
Anthony P Monaco
International Molecular Genetic Study of Autism Consortium (IMGSAC)
Publication date
01-12-2010
Publisher
BioMed Central
Published in
Molecular Autism / Issue 1/2010
Electronic ISSN: 2040-2392
DOI
https://doi.org/10.1186/2040-2392-1-7

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