[HTML][HTML] The foundation and architecture of precision medicine in neurology and psychiatry
Neurological and psychiatric diseases have high degrees of genetic and pathophysiological
heterogeneity, irrespective of clinical manifestations. Traditional medical paradigms have …
heterogeneity, irrespective of clinical manifestations. Traditional medical paradigms have …
[HTML][HTML] Phase separation as a missing mechanism for interpretation of disease mutations
It is unclear how disease mutations impact intrinsically disordered protein regions (IDRs),
which lack a stable folded structure. These mutations, while prevalent in disease, are …
which lack a stable folded structure. These mutations, while prevalent in disease, are …
Rare coding variation provides insight into the genetic architecture and phenotypic context of autism
Some individuals with autism spectrum disorder (ASD) carry functional mutations rarely
observed in the general population. We explored the genes disrupted by these variants from …
observed in the general population. We explored the genes disrupted by these variants from …
Molecular and network-level mechanisms explaining individual differences in autism spectrum disorder
The mechanisms underlying phenotypic heterogeneity in autism spectrum disorder (ASD)
are not well understood. Using a large neuroimaging dataset, we identified three latent …
are not well understood. Using a large neuroimaging dataset, we identified three latent …
A phenotypic spectrum of autism is attributable to the combined effects of rare variants, polygenic risk and sex
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 …
combinations of genetic factors determine risk is unclear. In a large family sample, we show …
Neuronal defects in a human cellular model of 22q11. 2 deletion syndrome
Abstract 22q11. 2 deletion syndrome (22q11DS) is a highly penetrant and common genetic
cause of neuropsychiatric disease. Here we generated induced pluripotent stem cells from …
cause of neuropsychiatric disease. Here we generated induced pluripotent stem cells from …
[HTML][HTML] Insufficient evidence for “autism-specific” genes
Despite evidence that deleterious variants in the same genes are implicated across multiple
neurodevelopmental and neuropsychiatric disorders, there has been considerable interest …
neurodevelopmental and neuropsychiatric disorders, there has been considerable interest …
A framework for an evidence-based gene list relevant to autism spectrum disorder
Autism spectrum disorder (ASD) is often grouped with other brain-related phenotypes into a
broader category of neurodevelopmental disorders (NDDs). In clinical practice, providers …
broader category of neurodevelopmental disorders (NDDs). In clinical practice, providers …
Relating pathogenic loss-of-function mutations in humans to their evolutionary fitness costs
Causal loss-of-function (LOF) variants for Mendelian and severe complex diseases are
enriched in'mutation intolerant'genes. We show how such observations can be interpreted in …
enriched in'mutation intolerant'genes. We show how such observations can be interpreted in …
[HTML][HTML] A genetics-first approach to understanding autism and schizophrenia spectrum disorders: the 22q11. 2 deletion syndrome
Recently, increasing numbers of rare pathogenic genetic variants have been identified that
are associated with variably elevated risks of a range of neurodevelopmental outcomes …
are associated with variably elevated risks of a range of neurodevelopmental outcomes …