RT Journal Article
SR Electronic
T1 Both rare and common genetic variants contribute to autism in the Faroe Islands
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 363853
DO 10.1101/363853
A1 Claire S Leblond
A1 Freddy Cliquet
A1 Coralie Carton
A1 Guillaume Huguet
A1 Alexandre Mathieu
A1 Thomas Kergrohen
A1 Julien Buratti
A1 Nathalie Lemière
A1 Laurence Cuisset
A1 Thierry Bienvenu
A1 Anne Boland
A1 Jean-François Deleuze
A1 GenMed consortium
A1 Tormodur Stora
A1 Rannva Biskupstoe
A1 Jónrit Halling
A1 Guðrið Andorsdóttir
A1 Eva Billstedt
A1 Christopher Gillberg
A1 Thomas Bourgeron
YR 2018
UL http://biorxiv.org/content/early/2018/07/06/363853.abstract
AB 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 compared to controls had a higher burden of copy-number variants (p < 0.05), higher inbreeding status (p < 0.005) and higher load of homozygous deleterious variants (p < 0.01). 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. KIRELL3 and CNTNAP2) affecting autism-risk 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.Author summary Autism is characterized by problems in social communication and stereotyped behavior. To improve our understanding of the genetic architecture of autism, we studied a group of children and adolescents from the Faroe Islands, an isolated population living on archipelago located in the North Atlantic Ocean, halfway between Norway, Iceland and Scotland since the 9th century. The genetic profile of this small but genetically homogenous epidelmiological cohort of the Faroe individuals revealed that both rare and common genetic variants contribute to the susceptibility to autism. Our analysis supports the role of several genes previously associated with autism and points at new candidate genes involved in the neuronal connectivity of the brain. In summary, our analysis provides a comprehensive framework to analyze the complex heterogeneity of autism in order to improve the diagnostic, the care and the integration of individuals with autism.