Common genetic variants contribute to risk of rare severe neurodevelopmental disorders

MEK Niemi, HC Martin, DL Rice, G Gallone, S Gordon… - Nature, 2018 - nature.com
There are thousands of rare human disorders that are caused by single deleterious, protein-
coding genetic variants. However, patients with the same genetic defect can have different …

De novo mutations revealed by whole-exome sequencing are strongly associated with autism

SJ Sanders, MT Murtha, AR Gupta, JD Murdoch… - Nature, 2012 - nature.com
Multiple studies have confirmed the contribution of rare de novo copy number variations to
the risk for autism spectrum disorders,,. But whereas de novo single nucleotide variants …

Evidence for 28 genetic disorders discovered by combining healthcare and research data

J Kaplanis, KE Samocha, L Wiel, Z Zhang, KJ Arvai… - Nature, 2020 - nature.com
De novo mutations in protein-coding genes are a well-established cause of developmental
disorders. However, genes known to be associated with developmental disorders account …

Rare coding variants in ten genes confer substantial risk for schizophrenia

T Singh, T Poterba, D Curtis, H Akil, M Al Eissa… - Nature, 2022 - nature.com
Rare coding variation has historically provided the most direct connections between gene
function and disease pathogenesis. By meta-analysing the whole exomes of 24,248 …

Large-scale discovery of novel genetic causes of developmental disorders

Nature, 2015 - nature.com
Despite three decades of successful, predominantly phenotype-driven discovery of the
genetic causes of monogenic disorders, up to half of children with severe developmental …

Prevalence and architecture of de novo mutations in developmental disorders

Nature, 2017 - nature.com
The genomes of individuals with severe, undiagnosed developmental disorders are
enriched in damaging de novo mutations (DNMs) in developmentally important genes. Here …

A phenotypic spectrum of autism is attributable to the combined effects of rare variants, polygenic risk and sex

D Antaki, J Guevara, AX Maihofer, M Klein, M Gujral… - Nature …, 2022 - nature.com
The genetic etiology of autism spectrum disorder (ASD) is multifactorial, but how
combinations of genetic factors determine risk is unclear. In a large family sample, we show …

De novo mutations in regulatory elements in neurodevelopmental disorders

PJ Short, JF McRae, G Gallone, A Sifrim, H Won… - Nature, 2018 - nature.com
We previously estimated that 42% of patients with severe developmental disorders carry
pathogenic de novo mutations in coding sequences. The role of de novo mutations in …

Genome-wide changes in lncRNA, splicing, and regional gene expression patterns in autism

NN Parikshak, V Swarup, TG Belgard, M Irimia… - Nature, 2016 - nature.com
Autism spectrum disorder (ASD) involves substantial genetic contributions. These
contributions are profoundly heterogeneous but may converge on common pathways that …

Sporadic autism exomes reveal a highly interconnected protein network of de novo mutations

BJ O'Roak, L Vives, S Girirajan, E Karakoc, N Krumm… - Nature, 2012 - nature.com
It is well established that autism spectrum disorders (ASD) have a strong genetic
component; however, for at least 70% of cases, the underlying genetic cause is unknown …