Type

Journal Article

Authors

Sean Ennis
Andrew Green
Denis C. Shields
Naisha Shah
Louise Gallagher
Regina Regan
Jane Mcgrath
Judith M. Conroy
Alison Merikangas
Tiago Magalhaes
and 2 others

Subjects

Psychiatry

Topics
autism spectrum disorder candidate genes novel the autism spectrum disorder asd genome wide association odds ratio copy number variation genes society neuroscience single nucleotide polymorphisms genetics

A novel approach of homozygous haplotype sharing identifies candidate genes in autism spectrum disorder. (2012)

Abstract Autism spectrum disorder (ASD) is a highly heritable disorder of complex and heterogeneous aetiology. It is primarily characterized by altered cognitive ability including impaired language and communication skills and fundamental deficits in social reciprocity. Despite some notable successes in neuropsychiatric genetics, overall, the high heritability of ASD (~90%) remains poorly explained by common genetic risk variants. However, recent studies suggest that rare genomic variation, in particular copy number variation, may account for a significant proportion of the genetic basis of ASD. We present a large scale analysis to identify candidate genes which may contain low-frequency recessive variation contributing to ASD while taking into account the potential contribution of population differences to the genetic heterogeneity of ASD. Our strategy, homozygous haplotype (HH) mapping, aims to detect homozygous segments of identical haplotype structure that are shared at a higher frequency amongst ASD patients compared to parental controls. The analysis was performed on 1,402 Autism Genome Project trios genotyped for 1 million single nucleotide polymorphisms (SNPs). We identified 25 known and 1,218 novel ASD candidate genes in the discovery analysis including CADM2, ABHD14A, CHRFAM7A, GRIK2, GRM3, EPHA3, FGF10, KCND2, PDZK1, IMMP2L and FOXP2. Furthermore, 10 of the previously reported ASD genes and 300 of the novel candidates identified in the discovery analysis were replicated in an independent sample of 1,182 trios. Our results demonstrate that regions of HH are significantly enriched for previously reported ASD candidate genes and the observed association is independent of gene size (odds ratio 2.10). Our findings highlight the applicability of HH mapping in complex disorders such as ASD and offer an alternative approach to the analysis of genome-wide association data.
Collections Ireland -> University College Dublin -> Biomolecular and Biomedical Science Research Collection
Ireland -> Trinity College Dublin -> RSS Feeds
Ireland -> Trinity College Dublin -> Psychiatry (Scholarly Publications)
Ireland -> University College Dublin -> College of Science
Ireland -> Trinity College Dublin -> Psychiatry
Ireland -> Trinity College Dublin -> RSS Feeds
Ireland -> University College Dublin -> School of Biomolecular & Biomedical Science
Ireland -> Trinity College Dublin -> School of Medicine

Full list of authors on original publication

Sean Ennis, Andrew Green, Denis C. Shields, Naisha Shah, Louise Gallagher, Regina Regan, Jane Mcgrath, Judith M. Conroy, Alison Merikangas, Tiago Magalhaes and 2 others

Experts in our system

1
Sean Ennis
University College Dublin
Total Publications: 52
 
2
Andrew Green
University College Dublin
Total Publications: 25
 
3
Denis C. Shields
University College Dublin
Total Publications: 118
 
4
Naisha Shah
University College Dublin
Total Publications: 7
 
5
Louise Gallagher
Trinity College Dublin
Total Publications: 59
 
6
Regina Regan
University College Dublin
Total Publications: 10
 
7
Jane Mcgrath
Trinity College Dublin
Total Publications: 11
 
8
Judith Conroy
University College Dublin
Total Publications: 24
 
9
Tiago R Magalhaes
University College Dublin
Total Publications: 6