Dataset Information

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

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.

SUBMITTER: Leblond CS

PROVIDER: S-EPMC6341098 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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

Leblond Claire S CS Cliquet Freddy F Carton Coralie C Huguet Guillaume G Mathieu Alexandre A Kergrohen Thomas T Buratti Julien J Lemière Nathalie N Cuisset Laurence L Bienvenu Thierry T Boland Anne A Deleuze Jean-François JF Stora Tormodur T Biskupstoe Rannva R Halling Jónrit J Andorsdóttir Guðrið G Billstedt Eva E Gillberg Christopher C Bourgeron Thomas T

NPJ genomic medicine 20190121

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 (<i>p</i> <i>= ...[more]

PMID: 30675382

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Project description:BackgroundLanguage plays a major role in human behavior. For this reason, neurodevelopmental and psychiatric disorders in which linguistic ability is impaired could have a big impact on the individual's social interaction and general wellbeing. Such disorders tend to have a strong genetic component, but most past studies examined mostly the linguistic overlaps across these disorders; investigations into their genetic overlaps are limited. The aim of this study was to assess the potential genetic overlap between language impairment and broader behavioral disorders employing methods capturing both common and rare genetic variants.MethodsWe employ polygenic risk scores (PRS) trained on specific language impairment (SLI) to evaluate genetic overlap across several disorders in a large case-cohort sample comprising ~13,000 autism spectrum disorder (ASD) cases, including cases of childhood autism and Asperger's syndrome, ~15,000 attention deficit/hyperactivity disorder (ADHD) cases, ~3000 schizophrenia cases, and ~21,000 population controls. We also examine rare variants in SLI/language-related genes in a subset of the sample that was exome-sequenced using the SKAT-O method.ResultsWe find that there is little evidence for genetic overlap between SLI and ADHD, schizophrenia, and ASD, the latter being in line with results of linguistic analyses in past studies. However, we observe a small, significant genetic overlap between SLI and childhood autism specifically, which we do not observe for SLI and Asperger's syndrome. Moreover, we observe that childhood autism cases have significantly higher SLI-trained PRS compared to Asperger's syndrome cases; these results correspond well to the linguistic profiles of both disorders. Our rare variant analyses provide suggestive evidence of association for specific genes with ASD, childhood autism, and schizophrenia.ConclusionsOur study provides, for the first time, to our knowledge, genetic evidence for ASD subtypes based on risk variants for language impairment.

Project description:Over 200 georeferenced registered rephotographic compilations of the Faroe Islands are provided in this dataset. The position of each compilation is georeferenced and thus locatable on a map. Each compilation consists of a historical and a corresponding contemporary image showing the same scene. With steady object features, these two images of the same geolocation are aligned pixel accurately. In the summer of 2022, all contemporary images were photographed by A. Schaffland, while historical images were retrieved from the National Museum of Denmark collections. Images show Faroese landscape and cultural heritage sites, focusing on relevant areas when the historical images were taken, e.g., Kirkjubøur, Tórshavn, and Saksun. Historic images date from the end of the 19th century to the middle of the 20th century. The historical images were taken by scientists, surveyors, archaeologists, and painters. All historical images are in the public domain, have no known rights, or are shared under a CC license. The contemporary images by A. Schaffland are released under CC BY-NC-SA 4.0. The dataset is organized as a GIS project. Historic images, not already georeferenced, were referenced with street view services. All historical images were added to the GIS database, containing camera position, viewing direction, etc. Each compilation can be displayed as an arrow from the camera position along the view direction on a map. Contemporary images were registered to historical images using a specialized tool. None or only a suboptimal rephotograph could be taken for some historical images. These historical images are still added to the database together with all other original images, providing additional data for improvements in rephotography methods in the upcoming years. The resulting image pairs can be used in image registration, landscape change, urban development, and cultural heritage research. Further, the database can be used for public engagement in heritage and as a benchmark for further rephotography and time-series projects.

Dataset Information

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

Publications

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

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