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A high-resolution, global atlas of mortality of children under five years of age between 2000 and 2017 highlights subnational geographical inequalities in the distribution, rates and absolute counts of child deaths by age.

Superluminous supernova SN 2017egm has a complex light curve that is well modelled by successive collisions of a shockwave with dense circumstellar shells ejected by its massive progenitor star during the pair-instability pulsation stage. Such a scenario might be responsible for providing a power source for superluminous supernovae in general.

Solid organ transplant recipients are at increased risk of infectious disease and have unique molecular pathophysiology. Here the authors use host-microbe profiling to assess SARS-CoV-2 infection and immunity in solid organ transplant recipients, showing enhanced viral abundance, impaired clearance, and increased expression of innate immunity genes.

DiNardo et al. perform a phase 1b/2 clinical trial of telaglenastat (CB-839) in combination with azacytidine in persons with advanced myelodysplastic syndromes and report on the treatment safety and efficacy, including a definition of clinical responders.

In a phase 1 trial of patients with advanced systemic mastocytosis, avapritinib, a selective KIT inhibitor, was generally well tolerated, elicited durable clinical responses and led to reductions in mast cell disease burden.

Genome-wide association meta-analyses identify 26 risk loci for epilepsy, including 19 loci specific to genetic generalized epilepsy. Prioritized candidate genes implicate synaptic processes and overlap with targets of antiseizure medications.

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.

Hydrologic data collected from river gauges inform critical decisions for allocating water resources, conserving ecosystems and predicting the occurrence of droughts and floods. The current global river gauge network is biased towards large, perennial rivers, and strategic adaptations are needed to capture the full scope of rivers on Earth.

Thorough evaluation of CRISPR RNA-guided nucleases off-targets in cells is required for advancing gene therapies. Here the authors report SURRO-seq for the simultaneous investigation of thousands of off-target sites for therapeutic RNA-guided nucleases in cells.

Stig Bojesen, Georgia Chenevix-Trench, Alison Dunning and colleagues report common variants at the TERT-CLPTM1L locus associated with mean telomere length measured in whole blood. They also identify associations at this locus to breast or ovarian cancer susceptibility and report functional studies in breast and ovarian cancer tissue and cell lines.

Genetically encoded dopamine sensors have emerged as an alternative to voltammetry for in vivo dopamine measurements. Here, the authors compare these two methods directly, and document dopamine responses during Pavlovian conditioning across the striatum.

GvpU regulates spatial organization of gas vesicles in the bacterial cytosol through tunable interactions with the core gas vesicle shell protein and phase transition, enabling future opportunities for engineering of cellular buoyancy.

Analysis of HbA1c and FPG levels across 117 population-based studies demonstrates regional variation in prevalence of previously undiagnosed screen-detected diabetes using one or both measures and suggests that use of elevated FPG alone could underestimate diabetes prevalence in low- and middle-income countries.

Contrary to the view that urbanization is a major driver of the global rise in obesity, the global increase in body-mass index is shown to be mostly due to increases in the body-mass indexes of rural populations.

Sehgal et al. show that branch-specific dendritic plasticity mechanisms in the retrosplenial cortex link memories acquired close in time such that, unlike independent memories, linked memories are encoded by many of the same dendritic branches.

Mechanisms of inefficient vaccine protection against pathobionts such as S. aureus (SA) are still unclear. Here the authors show that prior SA exposure induces non-protective CD4⁺ T cells, which impair IsdB vaccine protection by IL-10 secretion and IL-17A suppression, whereas IL-17A promoting adjuvant CAF01 overcomes this dilemma.

Association analyses in over 1 million individuals identify 535 new loci influencing blood pressure traits. The results provide new insights into blood pressure regulation and highlight shared genetic architecture between blood pressure and lifestyle exposures.

Multi-ancestry meta-analyses of genome-wide association studies for self-reported physical activity during leisure time, leisure screen time, sedentary commuting and sedentary behavior at work identify 99 loci associated with at least one of these traits.

Lawson et al. show that genetic inactivation of Phd1 or Phd2 hinders progression of AML and compromises leukemic stem cells. They develop a selective PHD inhibitor IOX5 and show therapeutic efficacy in AML, which can be potentiated with venetoclax.

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.

The impact of other pathogens on disease outcome was studied in European infants with RSV infection. Additional viruses were commonly co-detected during infection but were weakly linked to severity. However, presence of Haemophilus bacteria strongly associated with severe cases.

Within-sibship genome-wide association analyses using data from 178,076 siblings illustrate differences between population-based and within-sibship GWAS estimates for phenotypes influenced by demographic and indirect genetic effects.

Fu, Mackowiak et al. show that cooperative action of the liver and the gut, rather than the liver alone, drives acetaldehyde clearance after alcohol consumption and modulates drinking behaviour.

Lineage plasticity is increasingly recognized as an emergent resistance mechanism after treatment with androgen receptor signalling inhibitors. To understand determinants of resistance, the authors analyzed the transcriptomes of patient tumor biopsies before enzalutamide treatment and at progression and identified a gene expression program associated with lineage plasticity risk and poor outcomes.

The lineage-specific receptor CSF1R controls macrophage development and homeostasis. Here the authors show that deletion of a conserved Csf1r enhancer (FIRE) selectively depletes brain microglia and resident macrophages in the epidermis, kidney, heart and peritoneum of otherwise healthy mice.

Data from over 700,000 individuals reveal the identity of 83 sequence variants that affect human height, implicating new candidate genes and pathways as being involved in growth.

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.

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.

An investigation using various methods reports an association between adeno-associated virus 2 and paediatric hepatitis of unknown aetiology.

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 FarmGTEx Project aims to understand genetic control of gene activity under diverse biological and environmental contexts in domestic animals, providing a foundation for improving animal precision breeding, adaptation and human health.

Integration of GWAS and single-cell transcriptomic data from the entire nervous system systematically identifies cell types underlying brain complex traits and provides insights into the etiology of Parkinson’s disease.

A dataset of coding variation, derived from exome sequencing of nearly one million individuals from a range of ancestries, provides insight into rare variants and could accelerate the discovery of disease-associated genes and advance precision medicine efforts.