Parent-Of-Origin Effects in Autism Identified through Genome-Wide Linkage Analysis of 16,000 SNPs
Published Date:Sep 02 2010
Source:PLoS One. 5(9).
Pubmed Central ID:PMC2932694
Funding:2P50HG003233/HG/NHGRI NIH HHS/United States
5U01DD000183/DD/NCBDD CDC HHS/United States
MH00219/MH/NIMH NIH HHS/United States
MH00980/MH/NIMH NIH HHS/United States
MH39437/MH/NIMH NIH HHS/United States
MH52708/MH/NIMH NIH HHS/United States
MH64547/MH/NIMH NIH HHS/United States
Autism is a common heritable neurodevelopmental disorder with complex etiology. Several genome-wide linkage and association scans have been carried out to identify regions harboring genes related to autism or autism spectrum disorders, with mixed results. Given the overlap in autism features with genetic abnormalities known to be associated with imprinting, one possible reason for lack of consistency would be the influence of parent-of-origin effects that may mask the ability to detect linkage and association.
Methods and Findings
We have performed a genome-wide linkage scan that accounts for potential parent-of-origin effects using 16,311 SNPs among families from the Autism Genetic Resource Exchange (AGRE) and the National Institute of Mental Health (NIMH) autism repository. We report parametric (GH, Genehunter) and allele-sharing linkage (Aspex) results using a broad spectrum disorder case definition. Paternal-origin genome-wide statistically significant linkage was observed on chromosomes 4 (LODGH = 3.79, empirical p<0.005 and LODAspex = 2.96, p = 0.008), 15 (LODGH = 3.09, empirical p<0.005 and LODAspex = 3.62, empirical p = 0.003) and 20 (LODGH = 3.36, empirical p<0.005 and LODAspex = 3.38, empirical p = 0.006).
These regions may harbor imprinted sites associated with the development of autism and offer fruitful domains for molecular investigation into the role of epigenetic mechanisms in autism.
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