Abstract
Autism spectrum disorder (ASD) has a strong but complex genetic component. Here we report on the resequencing of 64 candidate neurodevelopmental disorder risk genes in 5,979 individuals: 3,486 probands and 2,493 unaffected siblings. We find a strong burden of de novo point mutations for these genes and specifically implicate nine genes. These include CHD2 and SYNGAP1, genes previously reported in related disorders, and novel genes TRIP12 and PAX5. We also show that mutation carriers generally have lower IQs and enrichment for seizures. These data begin to distinguish genetically distinct subtypes of autism important for aetiological classification and future therapeutics.
| Original language | English (US) |
|---|---|
| Article number | 5595 |
| Journal | Nature Communications |
| Volume | 5 |
| DOIs | |
| State | Published - 2014 |
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ASJC Scopus subject areas
- Biochemistry, Genetics and Molecular Biology(all)
- Chemistry(all)
- Physics and Astronomy(all)
Cite this
Recurrent de novo mutations implicate novel genes underlying simplex autism risk. / O'Roak, Brian; Stessman, H. A.; Boyle, E. A.; Witherspoon, K. T.; Martin, B.; Lee, C.; Vives, L.; Baker, C.; Hiatt, J. B.; Nickerson, D. A.; Bernier, R.; Shendure, J.; Eichler, E. E.
In: Nature Communications, Vol. 5, 5595, 2014.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Recurrent de novo mutations implicate novel genes underlying simplex autism risk
AU - O'Roak, Brian
AU - Stessman, H. A.
AU - Boyle, E. A.
AU - Witherspoon, K. T.
AU - Martin, B.
AU - Lee, C.
AU - Vives, L.
AU - Baker, C.
AU - Hiatt, J. B.
AU - Nickerson, D. A.
AU - Bernier, R.
AU - Shendure, J.
AU - Eichler, E. E.
PY - 2014
Y1 - 2014
N2 - Autism spectrum disorder (ASD) has a strong but complex genetic component. Here we report on the resequencing of 64 candidate neurodevelopmental disorder risk genes in 5,979 individuals: 3,486 probands and 2,493 unaffected siblings. We find a strong burden of de novo point mutations for these genes and specifically implicate nine genes. These include CHD2 and SYNGAP1, genes previously reported in related disorders, and novel genes TRIP12 and PAX5. We also show that mutation carriers generally have lower IQs and enrichment for seizures. These data begin to distinguish genetically distinct subtypes of autism important for aetiological classification and future therapeutics.
AB - Autism spectrum disorder (ASD) has a strong but complex genetic component. Here we report on the resequencing of 64 candidate neurodevelopmental disorder risk genes in 5,979 individuals: 3,486 probands and 2,493 unaffected siblings. We find a strong burden of de novo point mutations for these genes and specifically implicate nine genes. These include CHD2 and SYNGAP1, genes previously reported in related disorders, and novel genes TRIP12 and PAX5. We also show that mutation carriers generally have lower IQs and enrichment for seizures. These data begin to distinguish genetically distinct subtypes of autism important for aetiological classification and future therapeutics.
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U2 - 10.1038/ncomms6595
DO - 10.1038/ncomms6595
M3 - Article
VL - 5
JO - Nature Communications
JF - Nature Communications
SN - 2041-1723
M1 - 5595
ER -