Search

Chronic care manages long-term, progressive conditions, while acute care handles short-term ones. Here, authors show chronic conditions account for most of the global health burden, with 68% of DALYs and 93% of YLDs attributed to chronic care needs.

An analysis of 24,202 critical cases of COVID-19 identifies potentially druggable targets in inflammatory signalling (JAK1), monocyte–macrophage activation and endothelial permeability (PDE4A), immunometabolism (SLC2A5 and AK5), and host factors required for viral entry and replication (TMPRSS2 and RAB2A).

A global network of researchers was formed to investigate the role of human genetics in SARS-CoV-2 infection and COVID-19 severity; this paper reports 13 genome-wide significant loci and potentially actionable mechanisms in response to infection.

Whole-genome sequencing, transcriptome-wide association and fine-mapping analyses in over 7,000 individuals with critical COVID-19 are used to identify 16 independent variants that are associated with severe illness in COVID-19.

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.

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.

Pooling participant-level genetic data into a single analysis can result in variance stratification, reducing statistical performance. Here, the authors develop variant-specific inflation factors to assess variance stratification and apply this to pooled individual-level data from whole genome sequencing.

Power exhaust is one of the biggest challenges stopping fusion energy. This article shows experimental evidence for strategically shaping the power exhaust region as a solution to this challenge, utilising physics understanding to strike a balance between engineering complexity and power exhaust benefits, consistent with reduced models and simulations.

A new resource for the analysis of population genomics and quantitative traits, the Drosophila melanogaster Genetic Reference Panel is presented.

Using data from a single time point, passenger-approximated clonal expansion rate (PACER) estimates the fitness of common driver mutations that lead to clonal haematopoiesis and identifies TCL1A activation as a mediator of clonal expansion.

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.

Chronic infection with SARS-CoV-2 leads to the emergence of viral variants that show reduced susceptibility to neutralizing antibodies in an immunosuppressed individual treated with convalescent plasma.

Sera from vaccinated individuals and some monoclonal antibodies show a modest reduction in neutralizing activity against the B.1.1.7 variant of SARS-CoV-2; but the E484K substitution leads to a considerable loss of neutralizing activity.

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.

Spatial orientation of cells in an interconnected network is lost in high-throughput single-cell epigenomic assays. Here the authors present sciMAP-ATAC to produce spatially resolved single-cell ATAC-seq data.

The Omicron variant evades vaccine-induced neutralization but also fails to form syncytia, shows reduced replication in human lung cells and preferentially uses a TMPRSS2-independent cell entry pathway, which may contribute to enhanced replication in cells of the upper airway. Altered fusion and cell entry characteristics are linked to distinct regions of the Omicron spike protein.

A study shows that clonal haematopoiesis of indeterminate potential is associated with an increased risk of chronic liver disease specifically through the promotion of liver inflammation and injury.

STAARpipeline is a comprehensive framework for flexible and scalable rare-variant association analysis using whole-genome sequencing data and annotation information.

A study of the evolution of the SARS-CoV-2 virus in England between September 2020 and June 2021 finds that interventions capable of containing previous variants were insufficient to stop the more transmissible Alpha and Delta variants.

Most studies of the genetics of the metabolome have been done in individuals of European descent. Here, the authors integrate genomics and metabolomics in Black individuals, highlighting the value of whole genome sequencing in diverse populations and linking circulating metabolites to human disease.

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.

Post-international travel quarantine has been widely implemented to mitigate SARS-CoV-2 transmission, but the impacts of such policies are unclear. Here, the authors used linked genomic and contact tracing data to assess the impacts of a 14-day quarantine on return to England in summer 2020.

In this study, Aggarwal and colleagues perform prospective sequencing of SARS-CoV-2 isolates derived from asymptomatic student screening and symptomatic testing of students and staff at the University of Cambridge. They identify important factors that contributed to within university transmission and onward spread into the wider community.

Intraspecies response to climate change is expected to align with genetic affinity. Using the American pika as a case study suggests that divisions of species distributions best explain intraspecific heterogeneity in climate relationships.

Platelet aggregation is associated with myocardial infarction and stroke. Here, the authors have conducted a whole genome sequencing association study on platelet aggregation, discovering a locus in RGS18, where enhancer assays suggest an effect on activity of haematopoeitic lineage transcription factors.

Analysis of 97,691 high-coverage human blood DNA-derived whole-genome sequences enabled simultaneous identification of germline and somatic mutations that predispose individuals to clonal expansion of haematopoietic stem cells, indicating that both inherited and acquired mutations are linked to age-related cancers and coronary heart disease.

Genetic and testing data from England show that the SARS-CoV-2 variant of concern B.1.1.7 has a transmission advantage over other lineages.

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.

Climate-smart agriculture (CSA) is an approach to the development of agricultural systems intended to help support food security under climate change. This Perspective outlines a set of CSA actions needed from public, private and civil society stakeholders: building evidence; increasing local institutional effectiveness; fostering coherence between climate and agricultural policies; and linking climate and agricultural financing.

The Eucalyptus grandis genome has been sequenced, revealing the greatest number of tandem duplications of any plant genome sequenced so far, and the highest diversity of genes for specialized metabolites that act as chemical defence and provide unique pharmaceutical oils; genome sequencing of the sister species E. globulus and a set of inbred E. grandis tree genomes reveals dynamic genome evolution and hotspots of inbreeding depression.

Common genetic variants associated with plasma lipids have been extensively studied for a better understanding of common diseases. Here, the authors use whole-genome sequencing of 16,324 individuals to analyze rare variant associations and to determine their monogenic and polygenic contribution to lipid traits.

Circulating lipoprotein(a) is an important risk factor for cardiovascular disease and shows variability between different ethnic groups. Here, Zekavat et al. perform whole-genome sequencing in individuals of European and African ancestries and find ancestry-specific genetic determinants for lipoprotein(a) levels.

MetaSTAAR enables functionally informed rare variant association analysis in biobank-scale cohorts using an efficient, sparse matrix approach for summary statistic storage.

Sven van der Lee, Julie Williams, Gerard Schellenberg and colleagues identify rare coding variants in PLCG2, ABI3 and TREM2 associated with Alzheimer's disease. These genes are highly expressed in microglia and provide additional evidence that the microglia-mediated immune response contributes to the development of Alzheimer's disease.

Until now, studies of evolution in the laboratory have primarily been carried out in asexual systems with small genomes, such as bacteria and yeast. Here, however, whole-genome resequencing data are presented from fruitfly populations that have experienced over 600 generations of laboratory selection for accelerated development. The results suggest that unconditionally advantageous alleles rarely arise, are associated with small net fitness gains, or cannot fix because selection coefficients change over time.

Philippe Amouyel, Julie Williams, Gerard Schellenberg, Sudha Seshadri and colleagues report a meta-analysis of genome-wide association studies for late-onset Alzheimer's disease in 17,008 cases and 37,154 controls with replication in an additional 8,572 cases and 11,312 controls. They identify 11 loci newly associated with Alzheimer's disease.

A high-resolution reference panel based on whole-genome sequencing data enables accurate imputation of HLA alleles across diverse populations and fine-mapping of HLA association signals for HIV-1 host response.

STAAR is a powerful rare variant association test that incorporates variant functional categories and complementary functional annotations using a dynamic weighting scheme based on annotation principal components. STAAR accounts for population structure and relatedness and is scalable for analyzing large whole-genome sequencing studies.