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A prospective nationwide genomic screening pilot for ten genes in young adults in Australia detected pathogenic variants in 2% of the population, most of whom were ineligible for government-funded genomic testing.

The Haiti earthquake ruptured one or more buried faults, generated tsunamis and caused extensive structural damage in Port-au-Prince. Investigations in the epicentral region quantify seismic hazards but offer no clear views of Haiti's seismic future.

Hydroxylamine oxidoreductase performs the second step in the oxidation of ammonium to nitrite, a critical part of the nitrogen cycle. Its structure reveals a complex arrangement of haems that could serve to direct electrons along two separate pathways.

Fine-mapping of causal variants and integration of epigenetic and chromatin conformation data identify likely target genes for 150 breast cancer risk regions.

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).

Parity induces an accumulation of CD8⁺ T cells, including cells with a tissue-resident-memory-like phenotype within human normal breast tissue, offering long-term protection against triple-negative breast cancer.

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.

The advantage of living in cities compared with rural areas with respect to height and BMI in children and adolescents has generally become smaller globally from 1990 to 2020, except in sub-Saharan Africa.

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.

Tracking data from 17 marine predator species in the Southern Ocean are used to identify Areas of Ecological Significance, the protection of which could help to mitigate increasing pressures on Southern Ocean ecosystems.

Previous work has identified several genes where mutations lead to breast cancer, but other genetic and environmental factors must still be accounted for. A large study of genetic association with breast cancer points to four novel genes and many more genetic markers that should be pursued for their link to cancer susceptibility.

High-resolution cryo-electron microscopy structure of smooth muscle myosin II in the inhibited state enables increased understanding of the functions of the head and tail regions in regulation of myosin activity and the pathological mechanisms of disease mutations.

A genome-wide association study of critically ill patients with COVID-19 identifies genetic signals that relate to important host antiviral defence mechanisms and mediators of inflammatory organ damage that may be targeted by repurposing drug treatments.

An artificial intelligence model defines a data-driven set of total parenteral nutrition compositions to assist clinicians in personalized treatment of neonates in intensive care and is able to adapt recommendations to patient status, with validation from large external cohorts and a blinded reader study.

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.

Exome sequencing and copy number analysis are used to define genomic aberrations in early sporadic pancreatic ductal adenocarcinoma; among the findings are mutations in genes involved in chromatin modification and DNA damage repair, and frequent and diverse somatic aberrations in genes known as embryonic regulators of axon guidance.

Roger Milne and colleagues conduct a genome-wide association study for estrogen receptor (ER)-negative breast cancer combined with BRCA1 mutation carriers in a large cohort. They identify ten new risk variants and find high genetic correlation between breast cancer risk for BRCA1 mutation carriers and risk of ER-negative breast cancer in the general population.

DNA methylation is associated with breast cancer risk. Here the authors measure DNA methylation in the blood of individuals from 25 Australian families with multiple cases of breast cancer but not known mutations associated with breast cancer risk to identify possible heritable methylation markers.

Openshaw and colleagues find myeloid inflammation and complement activation signatures in patients with long COVID who were previously hospitalized.

An analysis of the impact of logging intensity on biodiversity in tropical forests in Sabah, Malaysia, identifies a threshold of tree biomass removal below which logged forests still have conservation value.

Investigators found that denileukin diftitox, which targets the interleukin-2 receptor, achieves objective response rates in 44% of patients with cutaneous T-cell lymphoma, with a median duration of response of 7.8 months and 2% incidence of severe vascular leak syndrome. The inclusion of a placebo arm in the study revealed several additional interesting observations.

The Microarray Quality Control consortium pitted 36 teams against each other to evaluate methods for creating genomic classifiers, computational tools for interpreting gene expression profiles. The performance of the classifiers on blinded validation data—and metadata on the analytic methods—reveal the challenges facing the field.

The genomes of 102 primary pancreatic neuroendocrine tumours have been sequenced, revealing mutations in genes with functions such as chromatin remodelling, DNA damage repair, mTOR activation and telomere maintenance, and a greater-than-expected contribution from germ line mutations.

A cross-ancestry genome-wide association meta-analysis of amyotrophic lateral sclerosis (ALS) including 29,612 patients with ALS and 122,656 controls identifies 15 risk loci with distinct genetic architectures and neuron-specific biology.

A 51-minute-orbital-period, fully eclipsing binary system consisting of a star with a comparable temperature to that of the Sun but a 100 times greater density, accreting onto a white dwarf is reported.

A binary star merger has produced a white dwarf with a spin period of under 7 minutes, a magnetic field of 600 to 900 million gauss and a radius only slightly larger than that of our Moon.

Telomerase-independent telomere lengthening is a potential target for cancer therapy, but molecules specific to this pathway have remained elusive. Henson et al. show that DNA circles of (CCCTAA)_n are specific intermediates of alternative lengthening of telomeres and present a sensitive assay to detect them.

Primary biliary cirrhosis is an autoimmune liver disease with poor therapeutic options. Here Cordell et al. a perform meta-analysis of European genome-wide association studies identifying six novel risk loci and a number of potential therapeutic pathways.

Amyotrophic lateral sclerosis (ALS) is a rapidly progressing neurodegenerative disease. Here, Wray and colleagues identify association of the GPX3-TNIP1 locus with ALS using cross-ethnic meta-analyses.

This report by the Consortium for Refractive Error and Myopia uses gene-environment-wide interaction study (GEWIS) to identify genetic loci that affect environmental influence in myopia development, and identifies ethnic specific genetic loci that attribute to eye refractive errors.

B-RAF is mutated in a large proportion of melanomas, and the first small molecule inhibitor has recently been approved for melanoma treatment. Here, by exome sequencing melanoma samples, Shi and colleagues show that B-RAF is amplified in tumours that have acquired resistance to the B-RAF inhibitor vemurafenib.