4 documents found, page 1 of 1
The role of rare compound heterozygous events in autism spectrum disorder
Lin, Bochao Danae; Colas, Fabrice; Nijman, Isaac J.; Medic, Jelena; Brands, William; Parr, Jeremy R.; van Eijk, Kristel R.; Klauck, Sabine M.The identification of genetic variants underlying autism spectrum disorders (ASDs) may contribute to a better understanding of their underlying biology. To examine the possible role of a specific type of compound heterozygosity in ASD, namely, the occurrence of a deletion together with a functional nucleotide variant on the remaining allele, we sequenced 550 genes in 149 individuals with ASD and their deletion-...
Analysis of shared heritability in common disorders of the brain
Anttila, Verneri; Bulik-Sullivan, Brendan; Finucane, Hilary K.; Walters, Raymond K.; Bras, Jose; Duncan, Laramie; Escott-Price, ValentinaDisorders of the brain can exhibit considerable epidemiological comorbidity and often share symptoms, provoking debate about their etiologic overlap. We quantified the genetic sharing of 25 brain disorders from genome-wide association studies of 265,218 patients and 784,643 control participants and assessed their relationship to 17 phenotypes from 1,191,588 individuals. Psychiatric disorders share common varian...
Polygenic transmission disequilibrium confirms that common and rare variation a...
Weiner, Daniel J.; Wigdor, Emilie M.; Ripke, Stephan; Walters, Raymond K.; Kosmicki, Jack A.; Grove, Jakob; Samocha, Kaitlin E.Autism spectrum disorder (ASD) risk is influenced by common polygenic and de novo variation. We aimed to clarify the influence of polygenic risk for ASD and to identify subgroups of ASD cases, including those with strongly acting de novo variants, in which polygenic risk is relevant. Using a novel approach called the polygenic transmission disequilibrium test and data from 6,454 families with a child with ASD, ...
Genetic and functional analyses of SHANK2 mutations suggest a multiple hit mode...
Leblond, Claire S.; Heinrich, Jutta; Delorme, Richard; Proepper, Christian; Betancur, Catalina; Huguet, Guillaume; Konyukh, Marina; Chaste, PaulineAutism spectrum disorders (ASD) are a heterogeneous group of neurodevelopmental disorders with a complex inheritance pattern. While many rare variants in synaptic proteins have been identified in patients with ASD, little is known about their effects at the synapse and their interactions with other genetic variations. Here, following the discovery of two de novo SHANK2 deletions by the Autism Genome Project, we...