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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.

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.

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.

A genome-wide association meta-analysis study of blood lipid levels in roughly 1.6 million individuals demonstrates the gain of power attained when diverse ancestries are included to improve fine-mapping and polygenic score generation, with gains in locus discovery related to sample size.

Transancestral GWAS meta-analysis in 160,420 individuals identifies 139 loci associated with refractive error, including myopia. Newly identified genes implicate pathways involved in eye growth and light signaling cascades.

The efficacy of photodynamic therapy is highly dependent on light delivery to activate a photosensitizer. Here the authors report AI-enabled, implantable, multichannel wireless telemetry for photodynamic therapy to enable uniform delivery of multi-wavelength light to tumors.

This study introduces the Cattle Cell Atlas, a single-cell expression resource including 1,793,854 cells from 59 tissues. Integrative analyses leveraging this atlas provide insights into the biology underlying bovine monogenic and complex traits.

This meta-analysis of genome-wide association studies identifies four genetic loci associated with circulating leptin levels independent of adiposity. Examination in mouse adipose tissue explants provides functional support for the leptin-associated loci.

In this Case Study, Drs Flossmann and Jayne describe the treatment of a patient with refractory Wegener's granulomatosis and discuss the challenges associated with managing this disorder.

A subset of pediatric gliomas harbour alterations in fibroblast growth factor receptor (FGFR)-family proteins. Here, the authors characterise the genomic landscape of 11,635 gliomas across ages and use isogenic model systems to explore the underlying biology of FGFR1-altered gliomas and potential therapeutic vulnerabilities.

After decades during which little has changed with respect to the therapeutic options available to clinicians treating patients with lupus nephritis, the use of targeted biologic agents is emerging as a possible treatment strategy. The authors discuss the potential of these agents, including both B-cell-directed and T-cell-directed therapies, and consider the specific circumstances in which they should be used, either alone or combined with conventional or other new therapies.

Clatworthy and colleagues examine adult nasal lymphoid tissues in response to SARS-CoV-2 infection. Longitudinal profiling reveals changes in barrier tissue to block viral entry beyond the epithelial cell layer and how tissue repair occurred after viral infection.

Strontium isotope analysis can be applied to animal and plant tissues to help determine their provenance. Here, the authors generate a strontium isoscape of sub-Saharan Africa using data from 2266 environmental samples and demonstrate its efficacy by tracing the African roots of individuals from historic slavery contexts.

Stereotactic needle biopsies are currently performed for diagnosis only in glioblastoma; this study highlights the depth of information available through multi-omics analysis.

This Review discusses the advances and challenges of managing antineutrophil cytoplasmic antibody-associated vasculitis. The authors discuss current treatment options, emerging therapies and unmet needs in the management of this disease.

RH5, which is part of the trimeric RCR-complex essential for invasion, is a vaccine candidate for malaria. Here, Williams et al. show that monoclonal antibodies targeting each of the three proteins in the RCR-complex can work together to more effectively block the invasion of red blood cells by Plasmodium falciparum and design a combination vaccine candidate.

The clinical course of chronic lymphocytic leukaemia (CLL) is variable and difficult to predict. Here, the authors conduct a genome wide association study meta-analysis for time to first treatment in CLL patients and report two loci associating with progressive disease.

The development of novel immunotherapies has improved treatment options for several immune-mediated diseases; however, outcomes for patients with immune-mediated kidney disease remain poor. In this Review, Hans-Joachim Anders, David Jayne and Brad Rovin suggest that this lack of progress relates to shortcomings in the approaches used to identify targets and measure outcomes. They discuss seven hurdles to the validation of therapeutic targets in immune-mediated kidney diseases and describe how these hurdles can be overcome to appropriately assess and introduce immunologic therapies for immune-mediated kidney disease.

Lupus nephritis is the most common severe manifestation of the autoimmune disease systemic lupus erythematosus. Although conventional immunosuppressive therapy can increase survival, this approach is associated with considerable adverse effects. In this Review, Gregersen and Jayne discuss the available and future approaches to deplete B-cell populations and the current evidence for the therapeutic use of B cell depletion therapies in lupus nephritis, derived from case studies and clinical trials.

Chronic lymphocytic leukaemia has a hereditary component, much of which remains to be identified. Here, the authors perform a genome-wide association study and find new risk loci for the disease, which are associated with genes involved in immune function.

Primary open-angle glaucoma (POAG) is highly heritable, yet not well understood from a genetic perspective. Here, the authors perform a meta-analysis of genome-wide association studies in 34,179 POAG cases, identifying 44 previously unreported risk loci and mapping effects across multiple ethnicities.

An exciting genome-wide association study in the British population for seven common diseases. This analysis confirms previously identified loci and provides strong evidence for many novel disease susceptibility loci.

A global dataset of the satellite-tracked movements of pelagic sharks and fishing fleets show that sharks—and, in particular, commercially important species—have limited spatial refuge from fishing effort.

A new study shows that chimpanzees possess a highly diverse culture of termite fishing that differs strongly among groups. Individuals copy group-specific techniques, and their combinations, with high conformity to maintain a unique group culture.

Environmental variability is one potential driver of behavioural and cultural diversity in humans and other animals. Here, the authors show that chimpanzee behavioural diversity is higher in habitats that are more seasonal and historically unstable, and in savannah woodland relative to forested sites.

Frequencies of rare variants fluctuate over populations, hampering gene discovery. Here the authors use a population-specific reference panel, the Genome of the Netherlands, to discover four novel loci involved in lipid metabolism, including an exonic variant in ABCA6.

Thousands of plants are known to be edible, yet we lack nutritional data for many of them. This study predicts the B-vitamin profiles for edible plants and finds many have the potential to help alleviate deficiencies and should be conservation priorities.

New laboratory studies using a simplified food web show that quantum dots can be ingested by certain ciliates and transferred to higher trophic organisms such as the predatory rotifers by dietary uptake.

Here authors show that machine learning derives the degree of background retinal pigmentation with more nuance than self-described ethnicity. Retinal pigment scores are associated with genes linked to melanin and may improve algorithmic fairness.

Vaccination is effective in protecting from COVID-19. Here the authors report immune responses and breakthrough infections in twice-vaccinated patients receiving anti-TNF treatments for inflammatory bowel disease, and find dampened vaccine responses that implicate the need of adapted vaccination schedules for these patients.

PPM1D is a known mediator of p53 signalling, and has been linked to treatment resistance in glioma. In this work, the authors utilise genomics, proteomics, and mouse models to determine the role of PPM1D in the development of diffuse midline glioma.

Structural variants (SVs) are prevalent in genomes of the general population. Here, Guryev and The Genome of the Netherlands Consortium describe the reference panel of haplotype-resolved SVs from 769 individuals from 250 Dutch families and show its utility for studying heritable traits.

Paul de Bakker, Cisca Wijmenga and colleagues report on The Genome of the Netherlands Project, including whole-genome sequencing of 769 individuals of Dutch ancestry from 250 parent-offspring families and construction of a phased haplotype map. Their intermediate-coverage population sequencing data set provides a complementary resource to other publicly available data sets, including the 1000 Genomes Project.

ANCA-associated vasculitis (AAV) includes three disease subtypes with partly overlapping clinical manifestations: granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA) and eosinophilic granulomatosis with polyangiitis (EGPA). This Review article provides an update on the diagnosis and classification of AAV, discussing parameters for assessing disease activity and predicting outcomes towards a personalized medicine approach.