AI Article Synopsis
- Research identifies distinct genetic subtypes of autism spectrum disorder (ASD) by analyzing physical traits, categorizing 325 Canadian children with ASD into dysmorphic and nondysmorphic groups.
- A novel genome-wide rare variant score (GRVS) was developed to assess genetic variants, revealing that children with dysmorphic ASD exhibit significantly higher GRVS than those without physical anomalies.
- Additional analysis using a polygenic transmission test showed that common ASD variants are more prevalent in nondysmorphic probands, supporting a new classification approach based on morphology to guide treatment strategies.
Article Abstract
Defining different genetic subtypes of autism spectrum disorder (ASD) can enable the prediction of developmental outcomes. Based on minor physical and major congenital anomalies, we categorize 325 Canadian children with ASD into dysmorphic and nondysmorphic subgroups. We develop a method for calculating a patient-level, genome-wide rare variant score (GRVS) from whole-genome sequencing (WGS) data. GRVS is a sum of the number of variants in morphology-associated coding and non-coding regions, weighted by their effect sizes. Probands with dysmorphic ASD have a significantly higher GRVS compared to those with nondysmorphic ASD (P = 0.03). Using the polygenic transmission disequilibrium test, we observe an over-transmission of ASD-associated common variants in nondysmorphic ASD probands (P = 2.9 × 10). These findings replicate using WGS data from 442 ASD probands with accompanying morphology data from the Simons Simplex Collection. Our results provide support for an alternative genomic classification of ASD subgroups using morphology data, which may inform intervention protocols.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9617891 | PMC |
| http://dx.doi.org/10.1038/s41467-022-34112-z | DOI Listing |
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