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

Lookup NU author(s): Dr Marc Woodbury-Smith, Dr Andrew Paterson



This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).


© 2018 The Author(s). 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.

Publication metadata

Author(s): Woodbury-Smith M, Paterson AD, O'Connor I, Zarrei M, Yuen RKC, Howe JL, Thompson A, Parlier M, Fernandez B, Piven J, Scherer SW, Vieland V, Szatmari P

Publication type: Article

Publication status: Published

Journal: Journal of Neurodevelopmental Disorders

Year: 2018

Volume: 10

Issue: 1

Online publication date: 11/06/2018

Acceptance date: 23/05/2018

Date deposited: 26/06/2018

ISSN (print): 1866-1947

ISSN (electronic): 1866-1956

Publisher: BioMed Central Ltd


DOI: 10.1186/s11689-018-9238-9


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