A Genetics-First Approach to Dissecting the Heterogeneity of Autism: Phenotypic Comparison of Autism Risk Copy Number Variants.

Objective: Certain copy number variants (CNVs) greatly increase the risk of autism. The authors conducted a genetics-first study to investigate whether heterogeneity in the clinical presentation of autism is underpinned by specific genotype-phenotype relationships.

Methods: This international study included 547 individuals (mean age, 12.

Treatment-resistant schizophrenia: current insights on the pharmacogenomics of antipsychotics.

Up to 30% of people with schizophrenia do not respond to two (or more) trials of dopaminergic antipsychotics. They are said to have treatment-resistant schizophrenia (TRS). Clozapine is still the only effective treatment for TRS, although it is underused in clinical practice.

Heritability of Autism Spectrum Disorder in a UK Population-Based Twin Sample.

Importance: Most evidence to date highlights the importance of genetic influences on the liability to autism and related traits. However, most of these findings are derived from clinically ascertained samples, possibly missing individuals with subtler manifestations, and obtained estimates may not be representative of the population.

Objectives: To establish the relative contributions of genetic and environmental factors in liability to autism spectrum disorder (ASD) and a broader autism phenotype in a large population-based twin sample and to ascertain the genetic/environmental relationship between dimensional trait measures and categorical diagnostic constructs of ASD.

Synaptic, transcriptional and chromatin genes disrupted in autism.

The genetic architecture of autism spectrum disorder involves the interplay of common and rare variants and their impact on hundreds of genes. Using exome sequencing, here we show that analysis of rare coding variation in 3,871 autism cases and 9,937 ancestry-matched or parental controls implicates 22 autosomal genes at a false discovery rate (FDR) < 0.05, plus a set of 107 autosomal genes strongly enriched for those likely to affect risk (FDR < 0.

Behavioral signatures related to genetic disorders in autism.

Background: Autism spectrum disorder (ASD) is well recognized to be genetically heterogeneous. It is assumed that the genetic risk factors give rise to a broad spectrum of indistinguishable behavioral presentations.

Methods: We tested this assumption by analyzing the Autism Diagnostic Interview-Revised (ADI-R) symptom profiles in samples comprising six genetic disorders that carry an increased risk for ASD (22q11.

Opening Pandora's box in the UK: a hypothetical pharmacogenetic test for clozapine.

Clozapine is a uniquely efficacious antipsychotic drug in treatment-resistant schizophrenia. Its use is restricted due to adverse effects including a rare but dangerous reduction in neutrophils (agranulocytosis) and the mandatory hematological monitoring this entails in many countries. We review the statistical, ethical and legal issues arising from a hypothetical pharmacogenetic test for clozapine, using the UK as an exemplary case for consideration.

Plasma, oral fluid, and whole-blood distribution of antipsychotics and metabolites in clinical samples.

Background: Oral fluid provides a noninvasive method of sample collection. The aim of this study was to obtain oral fluid, plasma, and whole blood from patients prescribed amisulpride, aripiprazole, clozapine, quetiapine, risperidone, or sulpiride and to measure plasma:whole blood and plasma:oral fluid analyte distribution.

Methods: Matched oral fluid, plasma and whole-blood samples were analyzed by liquid chromatography-tandem mass spectrometry.

Prader-Willi syndrome: intellectual abilities and behavioural features by genetic subtype.

Background: Studies of chromosome 15 abnormality have implicated over-expression of paternally imprinted genes in the 15q11-13 region in the aetiology of autism. To test this hypothesis we compared individuals with Prader-Willi syndrome (PWS) due to uniparental disomy (UPD--where paternally imprinted genes are over-expressed) to individuals with the 15q11-13 deletion form of the syndrome (where paternally imprinted genes are not over-expressed). We also tested reports that PWS cases due to the larger type I (TI) form of deletion show differences to cases with the smaller type II (TII) deletion.