A genome-wide linkage study of autism spectrum disorder and the broad autism phenotype in extended pedigrees

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  • Woodbury-Smith, Marc
    • Other Affiliation: Institute of Neuroscience, Newcastle University, Sir James Spence Institute, Royal Victoria Infirmary, Queen Victoria Road, Newcastle upon Tyne NE1 4LP, UK. Program in Genetics and Genome Biology, The Centre for Applied Genomics, The Hospital for Sick Children, Toronto, ON, Canada
  • Paterson, Andrew D
    • Other Affiliation: Program in Genetics and Genome Biology, The Centre for Applied Genomics, The Hospital for Sick Children, Toronto, ON, Canada. Division ofEpidemiology and Biostatistics, Dalla Lana School of Public Health, University of Toronto, Toronto, ON, Canada
  • O’Connor, Irene
    • Other Affiliation: Department of Psychiatry and BehaviouralNeurosciences, McMaster University, Hamilton, ON, Canada
  • Zarrei, Mehdi
    • Other Affiliation: Program in Genetics and Genome Biology, The Centre for AppliedGenomics, The Hospital for Sick Children, Toronto, ON, Canada
  • Yuen, Ryan K C
    • Other Affiliation: Program in Genetics and Genome Biology, The Centre for AppliedGenomics, The Hospital for Sick Children, Toronto, ON, Canada
  • Howe, Jennifer L
    • Other Affiliation: Program in Genetics and Genome Biology, The Centre for AppliedGenomics, The Hospital for Sick Children, Toronto, ON, Canada
  • Thompson, Ann
    • Other Affiliation: Department of Psychiatry and BehaviouralNeurosciences, McMaster University, Hamilton, ON, Canada
  • Parlier, Morgan
    • Affiliation: School of Medicine, Neurodevelopment Disorders Research Center, Carolina Institute for Developmental Disabilities
  • Fernandez, Bridget
    • Other Affiliation: Provincial MedicalGenetics Program, Health Sciences Centre, St. John’s, Newfoundland, Canada
  • Piven, Joseph
    • Affiliation: School of Medicine, Neurodevelopment Disorders Research Center, Carolina Institute for Developmental Disabilities
  • Scherer, Stephen W
    • Other Affiliation: Program in Genetics and Genome Biology, The Centre for AppliedGenomics, The Hospital for Sick Children, Toronto, ON, Canada; McLaughlin Centre and Department of Molecular Genetics, University ofToronto, Toronto, ON, Canada
  • Vieland, Veronica
    • Other Affiliation: Battelle Center for Mathematical Medicine,The Research Institute at Nationwide Children’s Hospital, Columbus, OH, USA
  • Szatmari, Peter
    • Other Affiliation: Centre for Addiction and Mental Health, The Hospital for Sick Children andUniversity of Toronto, Toronto, ON, Canada
Abstract
  • Background Although several genetic variants for autism spectrum disorder (ASD) have now been identified, these largely occur sporadically or are de novo. Much less progress has been made in identifying inherited variants, even though the disorder itself is familial in the majority of cases. The objective of this study was to identify chromosomal regions that harbor inherited variants increasing the risk for ASD using an approach that examined both ASD and the broad autism phenotype (BAP) among a unique sample of extended pedigrees. Methods ASD and BAP were assessed using standardized tools in 28 pedigrees from Canada and the USA, each with at least three ASD-diagnosed individuals from two nuclear families. Genome-wide linkage analysis was performed using the posterior probability of linkage (PPL) statistic, a quasi-Bayesian method that provides strength of evidence for or against linkage in an essentially model-free manner, with outcomes on the probability scale. Results The results confirm appreciable interfamilial heterogeneity as well as a high level of intrafamilial heterogeneity. Both ASD and combined ASD/BAP specific loci are apparent. Conclusions Inclusion of subclinical phenotypes such as BAP should be more widely employed in genetic studies of ASD as a way of identifying inherited genetic variants for the disorder. Moreover, the results underscore the need for approaches to identifying genetic risk factors in extended pedigrees that are robust to high levels of inter/intrafamilial locus and allelic heterogeneity.
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Resource type
  • Article
Rights statement
  • In Copyright
Rights holder
  • The Author(s).
Journal title
  • Journal of Neurodevelopmental Disorders
Journal volume
  • 10
Journal issue
  • 1
Page start
  • 20
Language
  • English
Bibliographic citation
  • Journal of Neurodevelopmental Disorders. 2018 Jun 11;10(1):20
Publisher
  • BioMed Central

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