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. 2010 Sep 2;5(9):e12513.
doi: 10.1371/journal.pone.0012513.

Parent-of-origin effects in autism identified through genome-wide linkage analysis of 16,000 SNPs

Delphine Fradin  1 , Keely Cheslack-Postava, Christine Ladd-Acosta, Craig Newschaffer, Aravinda Chakravarti, Dan E Arking, Andrew Feinberg, M Daniele Fallin
Affiliations

Parent-of-origin effects in autism identified through genome-wide linkage analysis of 16,000 SNPs

Delphine Fradin et al. PLoS One. .

Abstract

Background: 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 (LOD(GH) = 3.79, empirical p<0.005 and LOD(Aspex) = 2.96, p = 0.008), 15 (LOD(GH) = 3.09, empirical p<0.005 and LOD(Aspex) = 3.62, empirical p = 0.003) and 20 (LOD(GH) = 3.36, empirical p<0.005 and LOD(Aspex) = 3.38, empirical p = 0.006).

Conclusions: 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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Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.

Figures

Figure 1
Figure 1. Results of Genome-wide Linkage Analysis.
Panel A: Parametric results. Panel B: Allele sharing results. Maternal scores are shown in red; paternal scores are in blue; no-imprinting scores are shown in gray.
Figure 2
Figure 2. Multipoint Parametric and Allele-sharing LOD scores on Chromosomes 4, 15 and 20.
Maternal scores are shown in red; paternal scores are in blue.
See this image and copyright information in PMC

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