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description Publicationkeyboard_double_arrow_right Article , Other literature type 2023 United Kingdom, FrancePublisher:Springer Science and Business Media LLC Funded by:NIH | Large-Scale Evaluation of..., EC | AIMS-2-TRIALS, EC | CANDY +5 projectsNIH| Large-Scale Evaluation of the Effect of Rare Genetic Variants on Psychiatric Symptoms and Cognitive Ability ,EC| AIMS-2-TRIALS ,EC| CANDY ,CIHR ,WT ,ANR| INCEPTION ,WT| Common Variant Genetics of Autism and Autistic Traits (GWAS) Consortium ,EC| R2D2-MHThomas Rolland; Freddy Cliquet; Richard J. L. Anney; Clara Moreau; Nicolas Traut; Alexandre Mathieu; Guillaume Huguet; Jinjie Duan; Varun Warrier; Swan Portalier; Louise Dry; Claire S. Leblond; Elise Douard; Frédérique Amsellem; Simon Malesys; Anna Maruani; Roberto Toro; Anders D. Børglum; Jakob Grove; Simon Baron-Cohen; Alan Packer; Wendy K. Chung; Sébastien Jacquemont; Richard Delorme; Thomas Bourgeron;AbstractWhile over 100 genes have been associated with autism, little is known about the prevalence of variants affecting them in individuals without a diagnosis of autism. Nor do we fully appreciate the phenotypic diversity beyond the formal autism diagnosis. Based on data from more than 13,000 individuals with autism and 210,000 undiagnosed individuals, 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 individuals 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 individuals 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 individuals carrying these variants.
PURE Aarhus Universi... arrow_drop_down Fachrepositorium LebenswissenschaftenArticle . 2023Data sources: Fachrepositorium LebenswissenschaftenHAL Descartes; HAL-Pasteur; Mémoires en Sciences de l'Information et de la CommunicationArticle . 2023License: CC BYadd ClaimPlease grant OpenAIRE to access and update your ORCID works.This Research product is the result of merged Research products in OpenAIRE.
You have already added works in your ORCID record related to the merged Research product.This Research product is the result of merged Research products in OpenAIRE.
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For further information contact us at helpdesk@openaire.euAccess Routeshybrid 10 citations 10 popularity Top 10% influence Average impulse Top 10% Powered by BIP!more_vert PURE Aarhus Universi... arrow_drop_down Fachrepositorium LebenswissenschaftenArticle . 2023Data sources: Fachrepositorium LebenswissenschaftenHAL Descartes; HAL-Pasteur; Mémoires en Sciences de l'Information et de la CommunicationArticle . 2023License: CC BYadd ClaimPlease grant OpenAIRE to access and update your ORCID works.This Research product is the result of merged Research products in OpenAIRE.
You have already added works in your ORCID record related to the merged Research product.This Research product is the result of merged Research products in OpenAIRE.
You have already added works in your ORCID record related to the merged Research product.All Research productsarrow_drop_down <script type="text/javascript"> <!-- document.write('<div id="oa_widget"></div>'); document.write('<script type="text/javascript" src="https://www.openaire.eu/index.php?option=com_openaire&view=widget&format=raw&projectId=10.1038/s41591-023-02408-2&type=result"></script>'); --> </script>
For further information contact us at helpdesk@openaire.eudescription Publicationkeyboard_double_arrow_right Preprint 2021 FrancePublisher:Cold Spring Harbor Laboratory Funded by:WT | Common Variant Genetics o..., EC | AIMS-2-TRIALS, EC | CANDY +1 projectsWT| Common Variant Genetics of Autism and Autistic Traits (GWAS) Consortium ,EC| AIMS-2-TRIALS ,EC| CANDY ,ANR| INCEPTIONThomas Rolland; Freddy Cliquet; Richard J.L. Anney; Clara Moreau; Nicolas Traut; Alexandre Mathieu; Guillaume Huguet; Jinjie Duan; Varun Warrier; Swan Portalier; Louise Dry; Claire S. Leblond; Elise Douard; Frédérique Amsellem; Simon Malesys; Anna Maruani; Roberto Toro; Anders D. Børglum; Jakob Grove; Simon Baron-Cohen; Alan Packer; Wendy K. Chung; Sébastien Jacquemont; Richard Delorme; Thomas Bourgeron;ABSTRACTWhile 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 diversity beyond the formal autism diagnosis. Using data from more than 13,000 autistic individuals and 210,000 undiagnosed individuals, 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 individuals 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 individuals, 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 individuals to better delineate the effect of genetic variants beyond the categorical diagnosis. Data are available at https://genetrek.pasteur.fr/.
https://www.medrxiv.... arrow_drop_down add ClaimPlease grant OpenAIRE to access and update your ORCID works.This Research product is the result of merged Research products in OpenAIRE.
You have already added works in your ORCID record related to the merged Research product.This Research product is the result of merged Research products in OpenAIRE.
You have already added works in your ORCID record related to the merged Research product.All Research productsarrow_drop_down <script type="text/javascript"> <!-- document.write('<div id="oa_widget"></div>'); document.write('<script type="text/javascript" src="https://www.openaire.eu/index.php?option=com_openaire&view=widget&format=raw&projectId=10.1101/2021.02.12.21251621&type=result"></script>'); --> </script>
For further information contact us at helpdesk@openaire.eu1 citations 1 popularity Average influence Average impulse Average Powered by BIP!more_vert https://www.medrxiv.... arrow_drop_down add ClaimPlease grant OpenAIRE to access and update your ORCID works.This Research product is the result of merged Research products in OpenAIRE.
You have already added works in your ORCID record related to the merged Research product.This Research product is the result of merged Research products in OpenAIRE.
You have already added works in your ORCID record related to the merged Research product.All Research productsarrow_drop_down <script type="text/javascript"> <!-- document.write('<div id="oa_widget"></div>'); document.write('<script type="text/javascript" src="https://www.openaire.eu/index.php?option=com_openaire&view=widget&format=raw&projectId=10.1101/2021.02.12.21251621&type=result"></script>'); --> </script>
For further information contact us at helpdesk@openaire.eudescription Publicationkeyboard_double_arrow_right Other literature type , Article , Preprint 2019 France, United Kingdom, France, France, GermanyPublisher:Cold Spring Harbor Laboratory Funded by:NIH | OPERATION, SUPPORT AND ST..., NIH | Enhancing neuroimaging re..., NIH | Center for Reproducible N... +5 projectsNIH| OPERATION, SUPPORT AND STRATEGIC ENHANCEMENT OF THE NEUROSCIENCE INFORMATION FRAMEWORK ,NIH| Enhancing neuroimaging reusability through semantic enrichment ,NIH| Center for Reproducible Neuroimaging Computation (CRNC) ,ANR| GENMED ,EC| AIMS-2-TRIALS ,EC| COSYN ,NIH| Exposing the Deep Content of the Publication: Knowledge Extraction for Neuroimaging in Child Psychiatry ,ANR| INCEPTIONAnne Biton; Nicolas Traut; Jean-Baptiste Poline; Benjamin S. Aribisala; Mark E. Bastin; Robin Bülow; Simon R. Cox; Ian J. Deary; Masaki Fukunaga; Hans J. Grabe; Saskia P. Hagenaars; Ryota Hashimoto; Masataka Kikuchi; Susana Muñoz Maniega; Matthias Nauck; Natalie A. Royle; Alexander Teumer; Maria del C. Valdés Hernández; Uwe Völker; Joanna M. Wardlaw; Katharina Wittfeld; Hidenaga Yamamori; Alzheimer’s Disease Neuroimaging Initiative; Thomas Bourgeron; Roberto Toro;pmc: PMC7175006 , PMC7197382
AbstractWe analysed the genomic architecture of neuroanatomical diversity using magnetic resonance imaging and single nucleotide polymorphism (SNP) data from >26,000 individuals from the UK Biobank project and 5 other projects that had previously participated in the ENIGMA consortium. Our results confirm the polygenic architecture of neuroanatomical diversity, with SNPs capturing from 40% to 54% of regional brain volume variance. Chromosomal length correlated with the amount of phenotypic variance captured, r∼0.64 on average, suggesting that at a global scale causal variants are homogeneously distributed across the genome. At a local scale, SNPs within genes (∼51%) captured ∼1.5 times more genetic variance than the rest; and SNPs with low minor allele frequency (MAF) captured less variance than the rest: the 40% of SNPs with MAF<5% captured <1/4th of the genetic variance. We also observed extensive pleiotropy across regions, with an average genetic correlation of rG∼0.45. Genetic correlations were similar to phenotypic and environmental correlations, however, genetic correlations were often larger than phenotypic correlations for the left/right volumes of the same region. The heritability of differences in left/right volumes was generally not statistically significant, suggesting an important influence of environmental causes in the variability of brain asymmetry. Our code is available at https://github.com/neuroanatomy/genomic-architecture.
bioRxiv arrow_drop_down bioRxivPreprint . 2019Cerebral CortexArticle . 2020 . Peer-reviewedLicense: OUP Standard Publication ReuseData sources: Crossrefadd ClaimPlease grant OpenAIRE to access and update your ORCID works.This Research product is the result of merged Research products in OpenAIRE.
You have already added works in your ORCID record related to the merged Research product.This Research product is the result of merged Research products in OpenAIRE.
You have already added works in your ORCID record related to the merged Research product.All Research productsarrow_drop_down <script type="text/javascript"> <!-- document.write('<div id="oa_widget"></div>'); document.write('<script type="text/javascript" src="https://www.openaire.eu/index.php?option=com_openaire&view=widget&format=raw&projectId=10.1101/592337&type=result"></script>'); --> </script>
For further information contact us at helpdesk@openaire.euAccess RoutesGreen hybrid 20 citations 20 popularity Top 10% influence Average impulse Top 10% Powered by BIP!more_vert bioRxiv arrow_drop_down bioRxivPreprint . 2019Cerebral CortexArticle . 2020 . Peer-reviewedLicense: OUP Standard Publication ReuseData sources: Crossrefadd ClaimPlease grant OpenAIRE to access and update your ORCID works.This Research product is the result of merged Research products in OpenAIRE.
You have already added works in your ORCID record related to the merged Research product.This Research product is the result of merged Research products in OpenAIRE.
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description Publicationkeyboard_double_arrow_right Article , Other literature type 2023 United Kingdom, FrancePublisher:Springer Science and Business Media LLC Funded by:NIH | Large-Scale Evaluation of..., EC | AIMS-2-TRIALS, EC | CANDY +5 projectsNIH| Large-Scale Evaluation of the Effect of Rare Genetic Variants on Psychiatric Symptoms and Cognitive Ability ,EC| AIMS-2-TRIALS ,EC| CANDY ,CIHR ,WT ,ANR| INCEPTION ,WT| Common Variant Genetics of Autism and Autistic Traits (GWAS) Consortium ,EC| R2D2-MHThomas Rolland; Freddy Cliquet; Richard J. L. Anney; Clara Moreau; Nicolas Traut; Alexandre Mathieu; Guillaume Huguet; Jinjie Duan; Varun Warrier; Swan Portalier; Louise Dry; Claire S. Leblond; Elise Douard; Frédérique Amsellem; Simon Malesys; Anna Maruani; Roberto Toro; Anders D. Børglum; Jakob Grove; Simon Baron-Cohen; Alan Packer; Wendy K. Chung; Sébastien Jacquemont; Richard Delorme; Thomas Bourgeron;AbstractWhile over 100 genes have been associated with autism, little is known about the prevalence of variants affecting them in individuals without a diagnosis of autism. Nor do we fully appreciate the phenotypic diversity beyond the formal autism diagnosis. Based on data from more than 13,000 individuals with autism and 210,000 undiagnosed individuals, 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 individuals 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 individuals 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 individuals carrying these variants.
PURE Aarhus Universi... arrow_drop_down Fachrepositorium LebenswissenschaftenArticle . 2023Data sources: Fachrepositorium LebenswissenschaftenHAL Descartes; HAL-Pasteur; Mémoires en Sciences de l'Information et de la CommunicationArticle . 2023License: CC BYadd ClaimPlease grant OpenAIRE to access and update your ORCID works.This Research product is the result of merged Research products in OpenAIRE.
You have already added works in your ORCID record related to the merged Research product.This Research product is the result of merged Research products in OpenAIRE.
You have already added works in your ORCID record related to the merged Research product.All Research productsarrow_drop_down <script type="text/javascript"> <!-- document.write('<div id="oa_widget"></div>'); document.write('<script type="text/javascript" src="https://www.openaire.eu/index.php?option=com_openaire&view=widget&format=raw&projectId=10.1038/s41591-023-02408-2&type=result"></script>'); --> </script>
For further information contact us at helpdesk@openaire.euAccess Routeshybrid 10 citations 10 popularity Top 10% influence Average impulse Top 10% Powered by BIP!more_vert PURE Aarhus Universi... arrow_drop_down Fachrepositorium LebenswissenschaftenArticle . 2023Data sources: Fachrepositorium LebenswissenschaftenHAL Descartes; HAL-Pasteur; Mémoires en Sciences de l'Information et de la CommunicationArticle . 2023License: CC BYadd ClaimPlease grant OpenAIRE to access and update your ORCID works.This Research product is the result of merged Research products in OpenAIRE.
You have already added works in your ORCID record related to the merged Research product.This Research product is the result of merged Research products in OpenAIRE.
You have already added works in your ORCID record related to the merged Research product.All Research productsarrow_drop_down <script type="text/javascript"> <!-- document.write('<div id="oa_widget"></div>'); document.write('<script type="text/javascript" src="https://www.openaire.eu/index.php?option=com_openaire&view=widget&format=raw&projectId=10.1038/s41591-023-02408-2&type=result"></script>'); --> </script>
For further information contact us at helpdesk@openaire.eudescription Publicationkeyboard_double_arrow_right Preprint 2021 FrancePublisher:Cold Spring Harbor Laboratory Funded by:WT | Common Variant Genetics o..., EC | AIMS-2-TRIALS, EC | CANDY +1 projectsWT| Common Variant Genetics of Autism and Autistic Traits (GWAS) Consortium ,EC| AIMS-2-TRIALS ,EC| CANDY ,ANR| INCEPTIONThomas Rolland; Freddy Cliquet; Richard J.L. Anney; Clara Moreau; Nicolas Traut; Alexandre Mathieu; Guillaume Huguet; Jinjie Duan; Varun Warrier; Swan Portalier; Louise Dry; Claire S. Leblond; Elise Douard; Frédérique Amsellem; Simon Malesys; Anna Maruani; Roberto Toro; Anders D. Børglum; Jakob Grove; Simon Baron-Cohen; Alan Packer; Wendy K. Chung; Sébastien Jacquemont; Richard Delorme; Thomas Bourgeron;ABSTRACTWhile 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 diversity beyond the formal autism diagnosis. Using data from more than 13,000 autistic individuals and 210,000 undiagnosed individuals, 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 individuals 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 individuals, 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 individuals to better delineate the effect of genetic variants beyond the categorical diagnosis. Data are available at https://genetrek.pasteur.fr/.
https://www.medrxiv.... arrow_drop_down add ClaimPlease grant OpenAIRE to access and update your ORCID works.This Research product is the result of merged Research products in OpenAIRE.
You have already added works in your ORCID record related to the merged Research product.This Research product is the result of merged Research products in OpenAIRE.
You have already added works in your ORCID record related to the merged Research product.All Research productsarrow_drop_down <script type="text/javascript"> <!-- document.write('<div id="oa_widget"></div>'); document.write('<script type="text/javascript" src="https://www.openaire.eu/index.php?option=com_openaire&view=widget&format=raw&projectId=10.1101/2021.02.12.21251621&type=result"></script>'); --> </script>
For further information contact us at helpdesk@openaire.eu1 citations 1 popularity Average influence Average impulse Average Powered by BIP!more_vert https://www.medrxiv.... arrow_drop_down add ClaimPlease grant OpenAIRE to access and update your ORCID works.This Research product is the result of merged Research products in OpenAIRE.
You have already added works in your ORCID record related to the merged Research product.This Research product is the result of merged Research products in OpenAIRE.
You have already added works in your ORCID record related to the merged Research product.All Research productsarrow_drop_down <script type="text/javascript"> <!-- document.write('<div id="oa_widget"></div>'); document.write('<script type="text/javascript" src="https://www.openaire.eu/index.php?option=com_openaire&view=widget&format=raw&projectId=10.1101/2021.02.12.21251621&type=result"></script>'); --> </script>
For further information contact us at helpdesk@openaire.eudescription Publicationkeyboard_double_arrow_right Other literature type , Article , Preprint 2019 France, United Kingdom, France, France, GermanyPublisher:Cold Spring Harbor Laboratory Funded by:NIH | OPERATION, SUPPORT AND ST..., NIH | Enhancing neuroimaging re..., NIH | Center for Reproducible N... +5 projectsNIH| OPERATION, SUPPORT AND STRATEGIC ENHANCEMENT OF THE NEUROSCIENCE INFORMATION FRAMEWORK ,NIH| Enhancing neuroimaging reusability through semantic enrichment ,NIH| Center for Reproducible Neuroimaging Computation (CRNC) ,ANR| GENMED ,EC| AIMS-2-TRIALS ,EC| COSYN ,NIH| Exposing the Deep Content of the Publication: Knowledge Extraction for Neuroimaging in Child Psychiatry ,ANR| INCEPTIONAnne Biton; Nicolas Traut; Jean-Baptiste Poline; Benjamin S. Aribisala; Mark E. Bastin; Robin Bülow; Simon R. Cox; Ian J. Deary; Masaki Fukunaga; Hans J. Grabe; Saskia P. Hagenaars; Ryota Hashimoto; Masataka Kikuchi; Susana Muñoz Maniega; Matthias Nauck; Natalie A. Royle; Alexander Teumer; Maria del C. Valdés Hernández; Uwe Völker; Joanna M. Wardlaw; Katharina Wittfeld; Hidenaga Yamamori; Alzheimer’s Disease Neuroimaging Initiative; Thomas Bourgeron; Roberto Toro;pmc: PMC7175006 , PMC7197382
AbstractWe analysed the genomic architecture of neuroanatomical diversity using magnetic resonance imaging and single nucleotide polymorphism (SNP) data from >26,000 individuals from the UK Biobank project and 5 other projects that had previously participated in the ENIGMA consortium. Our results confirm the polygenic architecture of neuroanatomical diversity, with SNPs capturing from 40% to 54% of regional brain volume variance. Chromosomal length correlated with the amount of phenotypic variance captured, r∼0.64 on average, suggesting that at a global scale causal variants are homogeneously distributed across the genome. At a local scale, SNPs within genes (∼51%) captured ∼1.5 times more genetic variance than the rest; and SNPs with low minor allele frequency (MAF) captured less variance than the rest: the 40% of SNPs with MAF<5% captured <1/4th of the genetic variance. We also observed extensive pleiotropy across regions, with an average genetic correlation of rG∼0.45. Genetic correlations were similar to phenotypic and environmental correlations, however, genetic correlations were often larger than phenotypic correlations for the left/right volumes of the same region. The heritability of differences in left/right volumes was generally not statistically significant, suggesting an important influence of environmental causes in the variability of brain asymmetry. Our code is available at https://github.com/neuroanatomy/genomic-architecture.
bioRxiv arrow_drop_down bioRxivPreprint . 2019Cerebral CortexArticle . 2020 . Peer-reviewedLicense: OUP Standard Publication ReuseData sources: Crossrefadd ClaimPlease grant OpenAIRE to access and update your ORCID works.This Research product is the result of merged Research products in OpenAIRE.
You have already added works in your ORCID record related to the merged Research product.This Research product is the result of merged Research products in OpenAIRE.
You have already added works in your ORCID record related to the merged Research product.All Research productsarrow_drop_down <script type="text/javascript"> <!-- document.write('<div id="oa_widget"></div>'); document.write('<script type="text/javascript" src="https://www.openaire.eu/index.php?option=com_openaire&view=widget&format=raw&projectId=10.1101/592337&type=result"></script>'); --> </script>
For further information contact us at helpdesk@openaire.euAccess RoutesGreen hybrid 20 citations 20 popularity Top 10% influence Average impulse Top 10% Powered by BIP!more_vert bioRxiv arrow_drop_down bioRxivPreprint . 2019Cerebral CortexArticle . 2020 . Peer-reviewedLicense: OUP Standard Publication ReuseData sources: Crossrefadd ClaimPlease grant OpenAIRE to access and update your ORCID works.This Research product is the result of merged Research products in OpenAIRE.
You have already added works in your ORCID record related to the merged Research product.This Research product is the result of merged Research products in OpenAIRE.
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