Intellectual disability is associated with increased runs of homozygosity in simplex autism
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Intellectual disability (ID), often attributed to autosomal-recessive mutations, occurs in 40% of autism spectrum disorders (ASDs). For this reason, we conducted a genome-wide analysis of runs of homozygosity (ROH) in simplex ASD-affected families consisting of a proband diagnosed with ASD and at least one unaffected sibling. In these families, probands with an IQ ≤ 70 show more ROH than their unaffected siblings, whereas probands with an IQ > 70 do not show this excess. Although ASD is far more common in males than in females, the proportion of females increases with decreasing IQ. Our data do support an association between ROH burden and autism diagnosis in girls; however, we are not able to show that this effect is independent of low IQ. We have also discovered several autism candidate genes on the basis of finding (1) a single gene that is within an ROH interval and that is recurrent in autism or (2) a gene that is within an autism ROH block and that harbors a homozygous, rare deleterious variant upon analysis of exome-sequencing data. In summary, our data suggest a distinct genetic architecture for participants with autism and co-occurring intellectual disability and that this architecture could involve a role for recessively inherited loci for this autism subgroup.
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Recessive variants account for a small fraction of idiopathic ASD and developmental delay.
“Recessive variants account for a small fraction of idiopathic ASD (Gamsiz et al., 2013) and developmental delay, but they account for a larger proportion (up to 30%) of cases in consanguineous families (Martin et al., 2018).”
From Getting to the cores of autism (2019) · cites this paper as Gamsiz et al., 2013
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Self-citation
- Authors
- Gamsiz, E. D., Viscidi, E. W., Frederick, A. M., Nagpal, S., Sanders, S. J., Murtha, M. T., Schmidt, M., Triche, E. W., Geschwind, D. H., State, M. W., Istrail, S., Cook, E. H., Devlin, B., & Morrow, E. M.
- Affiliations
- Brown University (US)
- Yale University (US)
- University of California, Los Angeles (US)
- University of Illinois Chicago (US)
- University of Pittsburgh (US)
- Corresponding author
- Morrow, Eric M.
- ORCID
- Venue
- The American Journal of Human Genetics
- Publisher
- Elsevier BV
- Published
- 2013-07
- Volume
- 93
- Issue
- 1
- Pages
- 103-109
- ISSN
- 0002-9297 (ISSN-L)
- PMC
- PMC3710760
- OpenAlex
- W1973211018
- Cited by
- 79
- References
- 25
- Citations by year
- 2026: 1 · 2025: 1 · 2024: 13 · 2023: 4 · 2022: 6 · 2020: 3 · 2019: 7 · 2018: 10 · 2017: 6 · 2016: 8 · 2015: 10 · 2014: 9 · 2013: 1
- FWCI
- 5.12
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- The American Journal of Human Genetics (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- Funders
- National Institute of Mental Health (K23MH080954)
- National Institute of General Medical Sciences (P30GM103410, T32GM007601)
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (P50HD055782)
- Topics
- Life Sciences › Neuroscience › Cognitive Neuroscience › Autism Spectrum Disorder Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genomic variations and chromosomal abnormalities
- Keywords
- intellectual disability, autism spectrum disorder, runs of homozygosity, recessive inheritance, autism candidate genes, sex differences in autism, genetic architecture
- MeSH terms
- Child, Child Development Disorders, Pervasive, Chromosomes, Human, Female, Genetics, Population, Homozygote, Humans, Intelligence Tests, Male, Intellectual Disability, Pedigree, Phenotype, Sex Factors, Genetic Predisposition to Disease, Genetic Diseases, Inborn, Genetic Association Studies
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