ORCID Profile
0000-0003-4205-8828
Current Organisations
University of Montreal
,
Centre Hospitalier Universitaire Sainte-Justine
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Publisher: Springer Science and Business Media LLC
Date: 26-06-2023
DOI: 10.1038/S41591-023-02408-2
Abstract: While over 100 genes have been associated with autism, little is known about the prevalence of variants affecting them in in iduals without a diagnosis of autism. Nor do we fully appreciate the phenotypic ersity beyond the formal autism diagnosis. Based on data from more than 13,000 in iduals with autism and 210,000 undiagnosed in iduals, we estimated the odds ratios for autism associated to rare loss-of-function (LoF) variants in 185 genes associated with autism, alongside 2,492 genes displaying intolerance to LoF variants. In contrast to autism-centric approaches, we investigated the correlates of these variants in in iduals without a diagnosis of autism. We show that these variants are associated with a small but significant decrease in fluid intelligence, qualification level and income and an increase in metrics related to material deprivation. These effects were larger for autism-associated genes than in other LoF-intolerant genes. Using brain imaging data from 21,040 in iduals from the UK Biobank, we could not detect significant differences in the overall brain anatomy between LoF carriers and non-carriers. Our results highlight the importance of studying the effect of the genetic variants beyond categorical diagnosis and the need for more research to understand the association between these variants and sociodemographic factors, to best support in iduals carrying these variants.
Publisher: Cold Spring Harbor Laboratory
Date: 13-02-2021
DOI: 10.1101/2021.02.12.21251621
Abstract: While over a hundred genes are significantly associated with autism, little is known about the prevalence of variants affecting them in the general population. Nor do we fully appreciate the phenotypic ersity beyond the formal autism diagnosis. Using data from more than 13,000 autistic in iduals and 210,000 undiagnosed in iduals, we provide a gene-level map of the odds ratio for autism associated to rare loss-of-function (LoF) variants in 185 genes robustly associated with autism, alongside 2,492 genes displaying intolerance to LoF variants. In contrast to autism-centric approaches, we investigated the phenotype of undiagnosed in iduals heterozygous for such variants and show that they exhibit a decrease in fluid intelligence, qualification level and income, and an increase in material deprivation. These effects were larger for LoFs in autism-associated genes than in other LoF-intolerant genes and appeared largely independent of sex and polygenic scores for autism. Using brain imaging data from 21,049 UK-Biobank in iduals, we provide evidence for smaller cortical surface area and volume among carriers of LoFs in genes with high odds ratios for autism. Our gene-level map is a key resource to distinguish genes with high and low odds ratio for autism, and highlights the importance of including quantitative data on both diagnosed and undiagnosed in iduals to better delineate the effect of genetic variants beyond the categorical diagnosis. Data are available at genetrek.pasteur.fr/ .
Location: France
Location: Canada
Location: France
No related grants have been discovered for Douard Elise.