Parent-Of-Origin Effects in Autism Identified through Genome-Wide Linkage Analysis of 16,000 SNPs

Details

• Alternative Title:
  PLoS One
• Personal Author:
  Fradin, Delphine ; Cheslack-Postava, Keely ; Ladd-Acosta, Christine ; Newschaffer, Craig ; Chakravarti, Aravinda ; Arking, Dan E. ; Feinberg, Andrew ; Fallin, M. Daniele
• Description:
  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.
  
  
• Subjects:
  Adolescent Adult Autistic Disorder Child Chromosome Mapping Female Genetic Linkage Genetic Predisposition To Disease Genome-Wide Association Study Genomic Imprinting Humans Male Middle Aged Pedigree Polymorphism, Single Nucleotide Young Adult

  More +
• Source:
  PLoS One. 5(9).
• Pubmed ID:
  20824079
• Pubmed Central ID:
  PMC2932694
• Document Type:
  Journal Article
• 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
• Volume:
  5
• Issue:
  9
• Collection(s):
  Emerging Infectious Diseases CDC Public Access
• Main Document Checksum:
  urn:sha256:7096e49cd16fdebf35c1b578d83b6234fb527e10e04e4f7cb97b6daf507e1d06
• Download URL:
  https://stacks.cdc.gov/view/cdc/22903/cdc_22903_DS1.pdf
• File Type:
  [PDF - 404.12 KB ]