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Polygenic scores for body mass index and obesity constructed using data from 5 million people with different ancestries were associated with distinct weight gain trajectories from early childhood to adulthood.

MultiSTAAR provides a general and flexible statistical framework for functionally informed multi-trait rare variant analysis of biobank-scale sequencing studies by jointly analyzing multiple traits and incorporating annotation information.

In CHIP, somatic mutations in a hematopoietic stem cell lead to a clonal subpopulation of blood cells. Here, the authors perform a CHIP meta-EWAS to establish its epigenetic features and age-related outcomes.

Analyses of genome and exome sequencing data identify rare coding and structural variants associated with atrial fibrillation and highlight genetic links between atrial fibrillation and cardiomyopathies.

A large genome-wide association study of more than 5 million individuals reveals that 12,111 single-nucleotide polymorphisms account for nearly all the heritability of height attributable to common genetic variants.

Adaptor protein complex 4 (AP-4) deficiency causes a severe neurological disorder via an unknown mechanism. Here, the authors reveal cargo and machinery of the AP-4 transport pathway, and propose that AP-4 mediates spatial regulation of autophagy through peripheral delivery of ATG9A.

Although the common genetic variants contributing to blood lipid levels have been studied, the contribution of rare variants is less understood. Here, the authors perform a rare coding and noncoding variant association study of blood lipid levels using whole genome sequencing data.

Genome-wide analyses identify variants associated with sinus node dysfunction, distal conduction disease and pacemaker implantation, implicating ion channel function, cardiac developmental programs and sarcomeric structure in bradyarrhythmia susceptibility.

The goals, resources and design of the NHLBI Trans-Omics for Precision Medicine (TOPMed) programme are described, and analyses of rare variants detected in the first 53,831 samples provide insights into mutational processes and recent human evolutionary history.

Genome-wide association analyses identify 11 loci associated with native myocardial T1 time, a marker of interstitial fibrosis, providing insights into the pathways involved in myocardial fibrosis and myofibroblast cell state acquisition.

Analysis of whole-genome sequences of 25,465 individuals of European ancestry shows that rare variants contribute substantially to the heritability of height and body mass index.

A large-scale meta-analysis across eight biobank datasets identifies common genetic variants associated with mosaic loss of the X chromosome in female participants.

The influence of X chromosome genetic variation on blood lipids and coronary heart disease (CHD) is not well understood. Here, the authors analyse X chromosome sequencing data across 65,322 multi-ancestry individuals, identifying associations of the Xq23 locus with lipid changes and reduced risk of CHD and diabetes mellitus.

The QT interval is a heritable electrocardiographic measure associated with arrhythmia risk when prolonged. Here, the authors used a series of genetic analyses to identify genetic loci, pathways, therapeutic targets, and relationships with cardiovascular disease.

Accurate classification of genetic variants is critical for research and patient care. Here, the authors report that population-based associations between rare variants and quantitative endophenotypes for monogenic diseases can provide support for variant pathogenicity.

A multi-ancestry genetic meta-analysis identifies 12 new loci associated with preeclampsia and gestational hypertension and proposes the integration of polygenic scores and clinical factors for disease prediction

Analysis of whole-exome sequencing data from over 200,000 individuals in the UK Biobank provides new insights into the contribution of rare variants to cardiometabolic diseases and traits.

A genome-wide association study of thoracic aortic aneurysms and dissections (TAAD) in the Million Veteran Program identifies 17 new risk loci and demonstrates that the genetic architecture of TAAD mirrors that of other complex traits.

Clonal hematopoiesis, often caused by mutations in DNMT3A and TET2, is associated with blood cancer and coronary artery disease. Here, the authors conduct an epigenome-wide association study, finding that clonal hematopoiesis caused by DNMT3A vs. TET2 mutations has directionally opposing changes in DNA methylation profiles, with both promoting stem cell self-renewal.

de Vries, Conomos, Singh and Nicholson et al. identify two additional loci associated with coronary artery calcification (ARSE and MMP16) via a genome-wide association study in 22,400 participants from multiple ancestral groups and prove that ARSE is a mediator of vascular smooth muscle cell calcification and phenotype switching.

Adjusting for common variant polygenic scores improves yield in gene-based rare variant association tests for quantitative traits, particularly when using sparse mixed models or simple linear models as an alternative to dense mixed-model approaches.

Obsessive-compulsive disorder (OCD) is a neuropsychiatric disorder with symptoms including intrusive thoughts and time-consuming repetitive behaviors. Here Noh and colleagues identify genes enriched for functional variants associated with increased risk of OCD.

Michael Donovan et al. examine well-preserved remains of diverse insect-feeding and fungal damage on Patagonian fossil and extant material of the conifer Agathis. They report a suite of blotch mines, galls, scale-insect covers, and rust fungus that re-occur on the same host genus through time and space, showing the persistence of ecological guilds and possible host-tracking across major plate movements since the late Mesozoic.