Familial aggregation of quantitative autistic traits in multiplex versus simplex autism
Open accessAbstract
Recent research has suggested that the mode of inheritance for simplex autism (SA, one individual in the family affected) may be distinct from that for multiplex autism (MA, two or more individuals affected). Since sub clinical autistic traits have been observed in "unaffected" relatives of children with autism, we explored whether the distributions of such traits in families supported differential modes of genetic transmission for SA and MA autism. We measured patterns of familial aggregation of quantitative autistic traits (QAT) in children and parents in 80 SA families and 210 MA families, using the Social Responsiveness Scale. When considering all SA and MA siblings who scored below a uniform quantitative (clinical-level) severity threshold, MA brothers exhibited a distinct pathological shift in the distribution, compared to SA brothers (P < 0.0001). Such aggregation of QAT was also observed in fathers but not among females in MA families. Significant spousal correlations for QAT-suggestive of assortative mating-were observed in both SA and MA families, but neither group was characterized by a greater-than-chance level of concordant elevation among spousal pairs in this volunteer sample. Among male first degree relatives, there exist distinct patterns of QAT manifestation for simplex versus multiplex autism. These findings are consistent with the results of molecular genetic studies that have suggested differential modes of intergenerational transmission for SA and MA. Characterization of QAT and other endophenotypes among close relatives may be useful for reducing sample heterogeneity in future genetic and neurobiologic studies of autism.
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Recent family data based on the Social Responsiveness Scale suggest that the contribution from different types of genetic variation differs between simplex and multiplex autism.
“Recent family data based on the social responsiveness scale (SRS), which is a quantitative measure of autism-related features heavily weighted on social factors, suggests that this is indeed the case [40].”
From Genetics of autism spectrum disorders (2011) · cites this paper as [40]
Familial aggregation of subclinical autistic traits may occur only in multiplex families.
“familial aggregation of subclinical autistic traits may occur only in multiplex families”
From Autism risk factors: genes, environment, and gene-environment interactions (2012) · cites this paper as [18]
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- Authors
- Virkud, Y. V., Todd, R. D., Abbacchi, A. M., Zhang, Y., & Constantino, J. N.
- Affiliations
- Washington University in St. Louis (US)
- Corresponding author
- Constantino, John N.
- Venue
- American Journal of Medical Genetics Part B Neuropsychiatric Genetics
- Publisher
- Wiley
- Published
- 2008-07-10
- Volume
- 150B
- Issue
- 3
- Pages
- 328-334
- ISSN
- 1552-4841 (ISSN-L)
- 1552-485X
- PMC
- PMC2819431
- OpenAlex
- W1974652030
- Cited by
- 215
- References
- 25
- Citations by year
- 2026: 4 · 2025: 1 · 2024: 7 · 2023: 8 · 2022: 8 · 2021: 17 · 2020: 9 · 2019: 15 · 2018: 16 · 2017: 13 · 2016: 15 · 2015: 18 · 2014: 15 · 2013: 10 · 2012: 21
- FWCI
- 6.55
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- American Journal of Medical Genetics Part B Neuropsychiatric Genetics (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Autism Speaks
- National Institutes of Health
- National Institute of Mental Health (MH 64547, R01MH064547)
- National Institute of Child Health and Human Development
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (HD42541, R01HD042541)
- Topics
- Life Sciences › Neuroscience › Cognitive Neuroscience › Autism Spectrum Disorder Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
- Life Sciences › Neuroscience › Developmental Neuroscience › Williams Syndrome Research
- Keywords
- autism spectrum disorder, familial aggregation, mode of inheritance, Social Responsiveness Scale, endophenotypes, assortative mating, spousal concordance, first-degree relatives, sample heterogeneity, genetic transmission
- MeSH terms
- Autistic Disorder, Child, Child, Preschool, Family, Female, Humans, Male, Parents, Pedigree, Phenotype, Psychiatric Status Rating Scales, Social Behavior, Quantitative Trait, Heritable, Siblings
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