Genetically meaningful phenotypic subgroups in autism spectrum disorders

O. J. Veatch, J. Veenstra-Vanderweele, M. Potter, Margaret A Pericak-Vance, J. L. Haines

Research output: Contribution to journalArticle

29 Citations (Scopus)

Abstract

Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder with strong evidence for genetic susceptibility. However, the effect sizes for implicated chromosomal loci are small, hard to replicate and current evidence does not explain the majority of the estimated heritability. Phenotypic heterogeneity could be one phenomenon complicating identification of genetic factors. We used data from the Autism Diagnostic Interview-Revised, Autism Diagnostic Observation Schedule, Vineland Adaptive Behavior Scales, head circumferences, and ages at exams as classifying variables to identify more clinically similar subgroups of individuals with ASD. We identified two distinct subgroups of cases within the Autism Genetic Resource Exchange dataset, primarily defined by the overall severity of evaluated traits. In addition, there was significant familial clustering within subgroups (odds ratio, OR≈1.38-1.42, P<0.00001), and genotypes were more similar within subgroups compared to the unsubgrouped dataset (Fst=0.17±0.0.0009). These results suggest that the subgroups recapitulate genetic etiology. Using the same approach in an independent dataset from the Autism Genome Project, we similarly identified two distinct subgroups of cases and confirmed this severity-based dichotomy. We also observed evidence for genetic contributions to subgroups identified in the replication dataset. Our results provide more effective methods of phenotype definition that should increase power to detect genetic factors influencing risk for ASD.

Original languageEnglish
Pages (from-to)276-285
Number of pages10
JournalGenes, Brain and Behavior
Volume13
Issue number3
DOIs
StatePublished - Mar 1 2014

Fingerprint

Autistic Disorder
Psychological Adaptation
Genetic Predisposition to Disease
Cluster Analysis
Appointments and Schedules
Odds Ratio
Head
Genotype
Observation
Genome
Interviews
Phenotype
Autism Spectrum Disorder
Datasets

Keywords

  • ASD
  • Autism spectrum disorders
  • Biomarkers
  • Diagnosis
  • Differential
  • Genetics
  • Multivariate
  • Phenotypes
  • Phenotypic subgroups
  • Statistical analyses

ASJC Scopus subject areas

  • Behavioral Neuroscience
  • Genetics
  • Neurology

Cite this

Genetically meaningful phenotypic subgroups in autism spectrum disorders. / Veatch, O. J.; Veenstra-Vanderweele, J.; Potter, M.; Pericak-Vance, Margaret A; Haines, J. L.

In: Genes, Brain and Behavior, Vol. 13, No. 3, 01.03.2014, p. 276-285.

Research output: Contribution to journalArticle

Veatch, OJ, Veenstra-Vanderweele, J, Potter, M, Pericak-Vance, MA & Haines, JL 2014, 'Genetically meaningful phenotypic subgroups in autism spectrum disorders', Genes, Brain and Behavior, vol. 13, no. 3, pp. 276-285. https://doi.org/10.1111/gbb.12117
Veatch, O. J. ; Veenstra-Vanderweele, J. ; Potter, M. ; Pericak-Vance, Margaret A ; Haines, J. L. / Genetically meaningful phenotypic subgroups in autism spectrum disorders. In: Genes, Brain and Behavior. 2014 ; Vol. 13, No. 3. pp. 276-285.
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