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- Title
Both rare and common genetic variants contribute to autism in the Faroe Islands.
- Authors
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
- Abstract
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. Genetic correlates of autism in natives of remote islands: A study of the genetic architecture of autism among people living on the remote Faroe Islands highlights the role of both common and rare gene variants to autism. Claire Leblond from the Institut Pasteur in Paris, France, and colleagues profiled the genetics of 357 Faroese individuals, including 36 with autism, 136 of their relatives and 185 non-autistic controls. Similar to the findings of genetic studies of autism from elsewhere, the researchers discovered rare structural variants in known autism-associated genes and a few new candidate genes linked to brain function. However, unlike studies from larger mainland populations, they also showed that inbreeding on these remote islands increased the likelihood of carrying two copies of the point mutations that contribute to autism.
- Publication
NPJ Genomic Medicine, 2019, Vol 4, Issue 1, pN.PAG
- ISSN
2056-7944
- Publication type
Article
- DOI
10.1038/s41525-018-0075-2