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

In̂s Sousa, Taane Clark, Richard Holt, Alistair Pagnamenta, Erik Mulder, Ruud Minderaa, Anthony Bailey, Agatino Battaglia, Sabine Klauck, Fritz Poustka, Anthony Monaco

Research output: Contribution to journalArticle

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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.

Original languageEnglish
Article number7
JournalMolecular Autism
Volume1
Issue number1
DOIs
Publication statusPublished - 2010

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Leucine
Population
Genes
Interpersonal Relations
Cell Adhesion
Haplotypes
Nervous System
Single Nucleotide Polymorphism
Autism Spectrum Disorder
Case-Control Studies
Logistic Models
Communication

ASJC Scopus subject areas

  • Psychiatry and Mental health
  • Developmental Neuroscience
  • Developmental Biology
  • Molecular Biology

Cite this

Polymorphisms in leucine-rich repeat genes are associated with autism spectrum disorder susceptibility in populations of European ancestry. / Sousa, In̂s; Clark, Taane; Holt, Richard; Pagnamenta, Alistair; Mulder, Erik; Minderaa, Ruud; Bailey, Anthony; Battaglia, Agatino; Klauck, Sabine; Poustka, Fritz; Monaco, Anthony.

In: Molecular Autism, Vol. 1, No. 1, 7, 2010.

Research output: Contribution to journalArticle

Sousa, I, Clark, T, Holt, R, Pagnamenta, A, Mulder, E, Minderaa, R, Bailey, A, Battaglia, A, Klauck, S, Poustka, F & Monaco, A 2010, 'Polymorphisms in leucine-rich repeat genes are associated with autism spectrum disorder susceptibility in populations of European ancestry', Molecular Autism, vol. 1, no. 1, 7. https://doi.org/10.1186/2040-2392-1-7
Sousa, In̂s ; Clark, Taane ; Holt, Richard ; Pagnamenta, Alistair ; Mulder, Erik ; Minderaa, Ruud ; Bailey, Anthony ; Battaglia, Agatino ; Klauck, Sabine ; Poustka, Fritz ; Monaco, Anthony. / Polymorphisms in leucine-rich repeat genes are associated with autism spectrum disorder susceptibility in populations of European ancestry. In: Molecular Autism. 2010 ; Vol. 1, No. 1.
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