Both rare and common genetic variants contribute to autism in the Faroe Islands

Leblond, C. S. et al. (2019) Both rare and common genetic variants contribute to autism in the Faroe Islands. npj Genomic Medicine, 4, 1. (doi: 10.1038/s41525-018-0075-2) (PMID:30675382) (PMCID:PMC6341098)

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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.

Item Type:Articles
Additional Information:. This work was supported by the Institut Pasteur; Centre National de la Recherche Scientifique; the Assistance Publique—Hôpitaux de Paris; the University Paris Diderot; the Simons Foundation; the Fondation pour la Recherche Médicale [DBI20141231310]; the European Commission Horizon 2020 [COSYN]; The human brain project; the European Commission Innovative Medicines Initiative [EU-AIMS no. 115300]; the Cognacq-Jay foundation; the Bettencourt-Schueller foundation; the Orange foundation; the FondaMental foundation; the Conny-Maeva foundation; and the Agence Nationale de la Recherche (ANR) [SynPathy]. This research was supported by the Laboratory of Excellence GENMED (Medical Genomics) grant no. ANR-10-LABX0013, Bio-Psy and by the INCEPTION program ANR-16-CONV-0005, all managed by the ANR part of the Investment for the Future program.
Glasgow Author(s) Enlighten ID:Gillberg, Professor Christopher
Authors: Leblond, C. S., Cliquet, F., Carton, C., Huguet, G., Mathieu, A., Kergrohen, T., Buratti, J., Lemière, N., Cuisset, L., Bienvenu, T., Boland, A., Deleuze, J.-F., Stora, T., Biskupstoe, R., Halling, J., Andorsdóttir, G., Billstedt, E., Gillberg, C., and Bourgeron, T.
College/School:College of Medical Veterinary and Life Sciences > School of Health & Wellbeing > Mental Health and Wellbeing
Journal Name:npj Genomic Medicine
Publisher:Nature Research
ISSN (Online):2056-7944
Copyright Holders:Copyright © 2019 The Authors
First Published:First published in npj Genomic Medicine 4:1
Publisher Policy:Reproduced under a Creative Commons License

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