Search

Krach et al. dissect the molecular mechanism of the alternative splicing modulator Branaplam in Huntington’s disease. They show that the drug lowers mutant HTT protein levels and ameliorates alternative splicing pathology in an iPSC disease model.

A genome-wide association study for attention deficit/hyperactivity disorder (ADHD) identifies 12 loci and implicates neurodevelopmental pathways and conserved regions of the genome as being involved in underlying ADHD biology.

Gene discovery and polygenic predictions from a genome-wide association study of educational attainment in 1.1 million individuals.

The genetic basis of expressive vocabulary in children around 2 years old is poorly understood. Here, the authors show that a genetic variant near the ROBO2gene is associated with early language acquisition in the general population and highlight a potential genetic link between language-related common genetic variation and a linkage region for dyslexia, speech-sound disorder and reading.

Stephanie London, Martin Tobin and colleagues report meta-analyses of genome-wide association studies for forced vital capacity (FVC), a spirometric measure of pulmonary function that reflects lung volume. They identify six regions newly associated with FVC and demonstrate that candidate genes at these loci are expressed in lung tissue and primary lung cells.

Louise Wain, Ian Hall, Martin Tobin and colleagues report genome-wide association analyses of lung function, identifying 43 new signals associated with one or more lung function traits. A genetic risk score derived from these results was significantly associated with risk for chronic obstructive pulmonary disease in independent populations.

Autism Spectrum Disorder and Attention-Deficit/Hyperactivity Disorder are co-occurring neurodevelopmental conditions displaying strong, discordant polygenic associations with educational attainment. Here, the authors study genetic mechanisms underlying genome-wide correlation patterns across these traits.

A genome-wide association study in ~3 million individuals identifies 3,952 independent variants associated with educational attainment. A polygenic index explains 12–16% of variance for this trait and contributes to risk prediction for ten diseases.

Adolescence is often associated with heightened reward learning and impulsivity. Here the authors show in 742 people aged 9-18 that reward learning in fact remains stable with age, whilst punishment learning increases and action initiation decreases.

A genome-wide association study in more than 400,000 individuals identifies 139 new signals for lung function. These variants can predict chronic obstructive pulmonary disease in independent, transancestral cohorts.

A genetic study identifies hundreds of loci associated with risk tolerance and risky behaviors, finds evidence of substantial shared genetic influences across these phenotypes, and implicates genes involved in neurotransmission.

Ken Ong and colleagues report a genome-wide association study for age at menarche. They find LIN28B associated with age at menarche, as well as several traits related to onset of puberty in both females and males.

Genetic and environmental factors impact on lung function, important in the diagnosis of pulmonary diseases. Here the authors use imputation of genotypes to the 1000 Genomes Project reference panel to identify novel, low frequency variants associated with lung function.

Mitochondrial dysfunction is a contributing factor in Parkinson’s disease. Here the authors carry out a multilayered omics analysis of Parkinson’s disease patient-derived neuronal cells, which reveals a reversible hypometabolism mediated by α-ketoglutarate dehydrogenase deficiency, which is correlated with disease progression in the donating patients.

Martin Tobin and colleagues report a meta-analysis of 23 genome-wide association studies for pulmonary function. They identify 16 loci newly associated with variation in two cross-sectional measures of lung function, used to define airway obstruction and to grade the severity of obstruction.

Here, the authors reveal using single-cell RNA sequencing that Parkinson’s disease (PD) patient-derived neuronal cells show altered primary cilia morphology and signaling suggesting cilia dysfunction may underlie PD pathogenesis.

A genome-wide association study in 293,723 individuals identifies 74 genetic variants associated with educational attainment, which, although only explaining a small proportion of the variation in educational attainment, highlights candidate genes and pathways for further study.