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

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

Research output: Contribution to journalArticle

26 Citations (Scopus)

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 (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). 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.

Original languageEnglish (US)
Article numbere12513
Pages (from-to)1-8
Number of pages8
JournalPloS one
Volume5
Issue number9
DOIs
StatePublished - Nov 1 2010

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Autistic Disorder
Single Nucleotide Polymorphism
linkage (genetics)
Genes
Genome
genome
Chromosomes
Ports and harbors
Masks
National Institute of Mental Health (U.S.)
Health
Chromosomes, Human, Pair 4
Aptitude
Genome-Wide Association Study
mental health
genomic imprinting
autism
Epigenomics
genetic resources
epigenetics

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

Cite this

Fradin, D., Cheslack-Postava, K., Ladd-Acosta, C., Newschaffer, C., Chakravarti, A., Arking, D. E., ... Fallin, M. D. (2010). Parent-of-origin effects in autism identified through genome-wide linkage analysis of 16,000 SNPs. PloS one, 5(9), 1-8. [e12513]. https://doi.org/10.1371/journal.pone.0012513
Fradin, Delphine ; Cheslack-Postava, Keely ; Ladd-Acosta, Christine ; Newschaffer, Craig ; Chakravarti, Aravinda ; Arking, Dan E. ; Feinberg, Andrew ; Fallin, M. Daniele. / Parent-of-origin effects in autism identified through genome-wide linkage analysis of 16,000 SNPs. In: PloS one. 2010 ; Vol. 5, No. 9. pp. 1-8.
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Fradin, D, Cheslack-Postava, K, Ladd-Acosta, C, Newschaffer, C, Chakravarti, A, Arking, DE, Feinberg, A & Fallin, MD 2010, 'Parent-of-origin effects in autism identified through genome-wide linkage analysis of 16,000 SNPs', PloS one, vol. 5, no. 9, e12513, pp. 1-8. https://doi.org/10.1371/journal.pone.0012513

Parent-of-origin effects in autism identified through genome-wide linkage analysis of 16,000 SNPs. / Fradin, Delphine; Cheslack-Postava, Keely; Ladd-Acosta, Christine; Newschaffer, Craig; Chakravarti, Aravinda; Arking, Dan E.; Feinberg, Andrew; Fallin, M. Daniele.

In: PloS one, Vol. 5, No. 9, e12513, 01.11.2010, p. 1-8.

Research output: Contribution to journalArticle

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AU - Fradin, Delphine

AU - Cheslack-Postava, Keely

AU - Ladd-Acosta, Christine

AU - Newschaffer, Craig

AU - Chakravarti, Aravinda

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AU - Feinberg, Andrew

AU - Fallin, M. Daniele

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N2 - 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 (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). 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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Fradin D, Cheslack-Postava K, Ladd-Acosta C, Newschaffer C, Chakravarti A, Arking DE et al. Parent-of-origin effects in autism identified through genome-wide linkage analysis of 16,000 SNPs. PloS one. 2010 Nov 1;5(9):1-8. e12513. https://doi.org/10.1371/journal.pone.0012513