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.
Sousa
Inês
I
Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford OX3 7BN, UK. anthony.monaco@well.ox.ac.uk.
Clark
Taane G
TG
Holt
Richard
R
Pagnamenta
Alistair T
AT
Mulder
Erik J
EJ
Minderaa
Ruud B
RB
Bailey
Anthony J
AJ
Battaglia
Agatino
A
Klauck
Sabine M
SM
Poustka
Fritz
F
Monaco
Anthony P
AP