Genetic Investigation of Quantitative Traits Related to Autism: Use of Multivariate Polygenic Models with Ascertainment Adjustment
Open accessAbstract
Autism is a severe developmental disorder of unknown etiology but with evidence for genetic influences. Here, we provide evidence for a genetic basis of several quantitative traits that are related to autism. These traits, from the Broader Phenotype Autism Symptom Scale (BPASS), were measured in nuclear families, each ascertained through two probands affected by autism spectrum disorder. The BPASS traits capture the continuum of severity of impairments and may be more informative for genetic studies than are the discrete diagnoses of autism that have been used by others. Using a sample of 201 nuclear families consisting of a total of 694 individuals, we implemented multivariate polygenic models with ascertainment adjustment to estimate heritabilities and genetic and environmental correlations between these traits. Our ascertainment adjustment uses conditioning on the phenotypes of probands, requires no modeling of the ascertainment process, and is applicable to multiplex ascertainment and multivariate traits. This appears to be the first such implementation for multivariate quantitative traits. The marked difference between heritability estimates of the trait for language onset with and without an ascertainment adjustment (0.08 and 0.22, respectively) shows that conclusions are sensitive to whether or not an ascertainment adjustment is used. Among the five BPASS traits that were analyzed, the traits for social motivation and range of interest/flexibility show the highest heritability (0.19 and 0.16, respectively) and also have the highest genetic correlation (0.92). This finding suggests a shared genetic basis of these two traits and that they may be most promising for future gene mapping and for extending pedigrees by phenotyping additional relatives.
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Relaxed ADI-R criteria are sensitive and efficient for detecting ASD in various populations.
“These relaxed criteria have been shown to be both sensitive and efficient in detecting children with ASD in a variety of populations (de Bildt et al. 2013; Risi et al. 2006; Sung et al. 2005).”
From Using standardized diagnostic instruments to classify children with autism in the study to explore early development (2015) · cites this paper as Sung et al. 2005
Some proposals overlap and define relaxed ADI-R criteria for ASD as meeting cutoff on social or communication domain and being within two points of cutoff on the other domain.
“Some of these proposals overlap with one another (Risi et al. 2006; Sung et al. 2005) and define relaxed ADI-R criteria for ASD as meeting the cutoff score on the social deficits domain or communication deficits domain and being within two points of the cutoff score on the social or communication domain not met.”
From Using standardized diagnostic instruments to classify children with autism in the study to explore early development (2015) · cites this paper as Sung et al. 2005
Many proposals have been made to address ADI-R/ADOS discordance or to loosen ADI-R criteria so that they cover a wider ASD spectrum than Autistic Disorder.
“There have been numerous proposals to resolve ADI-R and ADOS discordance or relax ADI-R criteria to include the broader spectrum of ASD in addition to the formerly defined Autistic Disorder (IMGSAC 2001; Risi et al. 2006; Sung et al. 2005).”
From Using standardized diagnostic instruments to classify children with autism in the study to explore early development (2015) · cites this paper as Sung et al. 2005
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- Authors
- Sung, Y. J., Dawson, G., Munson, J., Estes, A., Schellenberg, G. D., & Wijsman, E. M.
- Affiliations
- University of Washington (US)
- Corresponding author
- Wijsman, Ellen M.
- Venue
- The American Journal of Human Genetics
- Publisher
- Elsevier BV
- Published
- 2005-01
- Volume
- 76
- Issue
- 1
- Pages
- 68-81
- ISSN
- 0002-9297 (ISSN-L)
- PMC
- PMC1196434
- OpenAlex
- W2023664755
- Cited by
- 113
- References
- 74
- Citations by year
- 2026: 4 · 2025: 1 · 2024: 2 · 2023: 3 · 2022: 3 · 2021: 8 · 2020: 4 · 2018: 2 · 2017: 3 · 2016: 4 · 2015: 4 · 2014: 5 · 2013: 12 · 2012: 5
- FWCI
- 3.69
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- The American Journal of Human Genetics (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- University of Washington
- National Institutes of Health
- National Institute on Deafness and Other Communication Disorders
- National Institute of General Medical Sciences (R01GM046255, R01 GM46255)
- National Institute of Child Health and Human Development
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (U19-HD35465, P01HD035465, U19HD035465)
- Topics
- Life Sciences › Neuroscience › Cognitive Neuroscience › Autism Spectrum Disorder Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
- Keywords
- autism spectrum disorder, heritability, genetic correlation, social motivation, flexibility, nuclear family, multiplex families, autism genetics
- MeSH terms
- Adolescent, Adult, Autistic Disorder, Child, Child, Preschool, Female, Multigene Family, Humans, Intelligence Tests, Male, Models, Genetic, Social Adjustment, Models, Statistical, Quantitative Trait, Heritable
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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