Both rare and common genetic variants contribute to autism in the Faroe Islands
The number of genes associated with autism is increasing, but few studies have been performed on epidemiological cohorts and in isolated populations. Here, we investigated 357 individuals from the Faroe Islands including 36 individuals with autism, 136 of their relatives and 185 non-autism controls....
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ftuglasgow:oai:eprints.gla.ac.uk:206485 2023-05-15T16:10:39+02:00 Both rare and common genetic variants contribute to autism in the Faroe Islands Leblond, Claire S Cliquet, Freddy Carton, Coralie Huguet, Guillaume Mathieu, Alexandre Kergrohen, Thomas Buratti, Julien Lemière, Nathalie Cuisset, Laurence Bienvenu, Thierry Boland, Anne Deleuze, Jean-François Stora, Tormodur Biskupstoe, Rannva Halling, Jónrit Andorsdóttir, Guðrið Billstedt, Eva Gillberg, Christopher Bourgeron, Thomas 2019-01-21 text http://eprints.gla.ac.uk/206485/ http://eprints.gla.ac.uk/206485/1/206485.pdf en eng Nature Research http://eprints.gla.ac.uk/206485/1/206485.pdf Leblond, C. S. et al. (2019) Both rare and common genetic variants contribute to autism in the Faroe Islands. npj Genomic Medicine <http://eprints.gla.ac.uk/view/journal_volume/npj_Genomic_Medicine.html>, 4, 1. (doi:10.1038/s41525-018-0075-2 <http://dx.doi.org/10.1038/s41525-018-0075-2>) (PMID:30675382) (PMCID:PMC6341098) cc_by_4 CC-BY Articles PeerReviewed 2019 ftuglasgow https://doi.org/10.1038/s41525-018-0075-2 2020-01-10T02:04:15Z The number of genes associated with autism is increasing, but few studies have been performed on epidemiological cohorts and in isolated populations. Here, we investigated 357 individuals from the Faroe Islands including 36 individuals with autism, 136 of their relatives and 185 non-autism controls. Data from SNP array and whole exome sequencing revealed that individuals with autism had a higher burden of rare exonic copy-number variants altering autism associated genes (deletions (p = 0.0352) or duplications (p = 0.0352)), higher inbreeding status (p = 0.023) and a higher load of rare homozygous deleterious variants (p = 0.011) compared to controls. Our analysis supports the role of several genes/loci associated with autism (e.g., NRXN1, ADNP, 22q11 deletion) and identified new truncating (e.g., GRIK2, ROBO1, NINL, and IMMP2L) or recessive deleterious variants (e.g., KIRREL3 and CNTNAP2) affecting autism-associated genes. It also revealed three genes involved in synaptic plasticity, RIMS4, KALRN, and PLA2G4A, carrying de novo deleterious variants in individuals with autism without intellectual disability. In summary, our analysis provides a better understanding of the genetic architecture of autism in isolated populations by highlighting the role of both common and rare gene variants and pointing at new autism-risk genes. It also indicates that more knowledge about how multiple genetic hits affect neuronal function will be necessary to fully understand the genetic architecture of autism. Article in Journal/Newspaper Faroe Islands University of Glasgow: Enlighten - Publications Faroe Islands npj Genomic Medicine 4 1 |
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University of Glasgow: Enlighten - Publications |
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ftuglasgow |
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English |
description |
The number of genes associated with autism is increasing, but few studies have been performed on epidemiological cohorts and in isolated populations. Here, we investigated 357 individuals from the Faroe Islands including 36 individuals with autism, 136 of their relatives and 185 non-autism controls. Data from SNP array and whole exome sequencing revealed that individuals with autism had a higher burden of rare exonic copy-number variants altering autism associated genes (deletions (p = 0.0352) or duplications (p = 0.0352)), higher inbreeding status (p = 0.023) and a higher load of rare homozygous deleterious variants (p = 0.011) compared to controls. Our analysis supports the role of several genes/loci associated with autism (e.g., NRXN1, ADNP, 22q11 deletion) and identified new truncating (e.g., GRIK2, ROBO1, NINL, and IMMP2L) or recessive deleterious variants (e.g., KIRREL3 and CNTNAP2) affecting autism-associated genes. It also revealed three genes involved in synaptic plasticity, RIMS4, KALRN, and PLA2G4A, carrying de novo deleterious variants in individuals with autism without intellectual disability. In summary, our analysis provides a better understanding of the genetic architecture of autism in isolated populations by highlighting the role of both common and rare gene variants and pointing at new autism-risk genes. It also indicates that more knowledge about how multiple genetic hits affect neuronal function will be necessary to fully understand the genetic architecture of autism. |
format |
Article in Journal/Newspaper |
author |
Leblond, Claire S Cliquet, Freddy Carton, Coralie Huguet, Guillaume Mathieu, Alexandre Kergrohen, Thomas Buratti, Julien Lemière, Nathalie Cuisset, Laurence Bienvenu, Thierry Boland, Anne Deleuze, Jean-François Stora, Tormodur Biskupstoe, Rannva Halling, Jónrit Andorsdóttir, Guðrið Billstedt, Eva Gillberg, Christopher Bourgeron, Thomas |
spellingShingle |
Leblond, Claire S Cliquet, Freddy Carton, Coralie Huguet, Guillaume Mathieu, Alexandre Kergrohen, Thomas Buratti, Julien Lemière, Nathalie Cuisset, Laurence Bienvenu, Thierry Boland, Anne Deleuze, Jean-François Stora, Tormodur Biskupstoe, Rannva Halling, Jónrit Andorsdóttir, Guðrið Billstedt, Eva Gillberg, Christopher Bourgeron, Thomas Both rare and common genetic variants contribute to autism in the Faroe Islands |
author_facet |
Leblond, Claire S Cliquet, Freddy Carton, Coralie Huguet, Guillaume Mathieu, Alexandre Kergrohen, Thomas Buratti, Julien Lemière, Nathalie Cuisset, Laurence Bienvenu, Thierry Boland, Anne Deleuze, Jean-François Stora, Tormodur Biskupstoe, Rannva Halling, Jónrit Andorsdóttir, Guðrið Billstedt, Eva Gillberg, Christopher Bourgeron, Thomas |
author_sort |
Leblond, Claire S |
title |
Both rare and common genetic variants contribute to autism in the Faroe Islands |
title_short |
Both rare and common genetic variants contribute to autism in the Faroe Islands |
title_full |
Both rare and common genetic variants contribute to autism in the Faroe Islands |
title_fullStr |
Both rare and common genetic variants contribute to autism in the Faroe Islands |
title_full_unstemmed |
Both rare and common genetic variants contribute to autism in the Faroe Islands |
title_sort |
both rare and common genetic variants contribute to autism in the faroe islands |
publisher |
Nature Research |
publishDate |
2019 |
url |
http://eprints.gla.ac.uk/206485/ http://eprints.gla.ac.uk/206485/1/206485.pdf |
geographic |
Faroe Islands |
geographic_facet |
Faroe Islands |
genre |
Faroe Islands |
genre_facet |
Faroe Islands |
op_relation |
http://eprints.gla.ac.uk/206485/1/206485.pdf Leblond, C. S. et al. (2019) Both rare and common genetic variants contribute to autism in the Faroe Islands. npj Genomic Medicine <http://eprints.gla.ac.uk/view/journal_volume/npj_Genomic_Medicine.html>, 4, 1. (doi:10.1038/s41525-018-0075-2 <http://dx.doi.org/10.1038/s41525-018-0075-2>) (PMID:30675382) (PMCID:PMC6341098) |
op_rights |
cc_by_4 |
op_rightsnorm |
CC-BY |
op_doi |
https://doi.org/10.1038/s41525-018-0075-2 |
container_title |
npj Genomic Medicine |
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4 |
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1 |
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