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Mutation profiling of pediatric cancers can help determine treatment options, however, large-scale datasets are rare. Here, the authors describe an institutional application of targeted sequencing to pediatric solid tumours, and identify potential therapeutic implications for identified mutations.

A genome-wide association study including over 76,000 individuals with schizophrenia and over 243,000 control individuals identifies common variant associations at 287 genomic loci, and further fine-mapping analyses highlight the importance of genes involved in synaptic processes.

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).

Plasma levels of liver enzymes provide insights into hepatic function and related diseases. Here, the authors perform a genome-wide association study on three liver enzymes, identifying genetic variants associated with their plasma concentration as well as links to metabolic and cardiovascular diseases.

The severity of ulcerative colitis, and response to treatment, is highly variable. Here, the authors examine rectal gene expression signatures and faecal microbiomes of children and adults with the disease and provide new insights in to pathogenesis.

HER2-low breast cancer has recently emerged as a targetable subset of breast tumors, for which the molecular landscape remains incompletely understood. Here, the authors use genomic data from 1039 patients to unveil and compare the genomic landscape of HER2-low and HER2-0 breast cancer.

In a cluster-randomized trial performed in 48 residential elderly care facilities in China, use of a low-sodium salt substitute instead of regular salt decreased blood pressure and cardiovascular events, whereas an alternative strategy of restricting salt consumption was not successful and did not have these beneficial effects.

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.

Safely opening university campuses has been a major challenge during the COVID-19 pandemic. Here, the authors describe a program of public health measures employed at a university in the United States which, combined with other non-pharmaceutical interventions, allowed the university to stay open in fall 2020 with limited evidence of transmission.

Dimethyl fumarate (DMF) is an anti-inflammatory drug proposed as a treatment for COVID19. Here the results are reported from a randomised trial testing DMF treatment in 713 patients hospitalised with COVID-19. DMF was not associated with any improvement in day 5 outcomes.

Cathy Laurie and colleagues detect mosaicism for large chromosomal abnormalities in peripheral blood in a subset of healthy individuals. They show that the frequency of such events increases with age and is associated with elevated risk of developing a subsequent hematological 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.

Astrocytes can respond to diseases and injuries of the central nervous system by driving the death of neurons and mature oligodendrocytes through the delivery of long-chain saturated fatty acids contained in lipoparticles.

One strategy to reduce the ecological footprint of food systems is to replace higher-emissions food products with lower-emissions alternatives. This study estimates the potential impact of product switches in Australia within ‘very similar’ and ‘less similar’ food categories in terms of greenhouse gas emissions and the nutritional quality and energy density of consumer purchases.

Ticks transmit a large number of pathogens that cause human diseases. Here, the authors sequence the genome of the tick Ixodes scapularisand uncover expansion of genes associated with parasitic processes unique to ticks and tick-host interactions.

Large whole-exome sequencing studies have suggested that the genetic architecture of syndromic congenital heart disease (CHD) is different from sporadic forms. Here, Watkins et al. estimate the relative contribution of damaging recessive and de novo genotypes to CHD in 2391 trios and find them to be associated with different gene functions.

Exome sequencing of 2,871 probands with congenital heart disease (CHD) provides new insights into the genetic architecture of these disorders. The results implicate new genes in CHD pathogenesis and highlight striking overlap between genes with damaging de novo mutations in individuals with CHD and autism.

Salt substitutes hold great potential for the control of blood pressure and prevention of chronic disease, but the evidence base remains inadequate. Data from a community-based trial in Peru add to this evidence base and support the conduct of large-scale trials to drive the global uptake of salt substitution.

Alzheimer’s disease has been associated with increased structural brain aging. Here the authors describe a model that predicts brain aging from resting state functional connectivity data, and demonstrate this is accelerated in individuals with pre-clinical familial Alzheimer’s disease.

The unprecedented cost of the 2018 eruption in Hawai’i reflects an intersection of disparate physical and social phenomena: widely spaced, highly destructive eruptions, and atypically high population growth. These were linked and the former indirectly drove the latter with unavoidable consequences.

Switchgrass engineered to express two enzymes that degrade the explosive hexahydro-1,3,5-trinitro-1,3,5-triazine (RDX) detoxifies military sites contaminated with the munition when grown on these plots in a 3-year field trial.

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.

Mutations in the Lbk1 tumour suppressor gene are found in the squamous carcinoma subtype of non-small cell lung cancers for the first time. In a mouse model for lung cancer in which Lkb1 loss is combined with Kras mutations, more aggressive tumours arise than with Kras mutations alone and often these are classified as squamous carcinomas, thus Lkb1 loss modulates lung cancer differentiation.

A large-scale study that analyses gene copy number changes in lung cancer identifies 31 recurrent focal events, which include amplification of the transcription factor NKX2.1 (also called TTF1), shown to act as an oncogene.

A meta-analysis of individual-level patient data from 66 clinical studies supports the utility of glomerular filtration rate as a surrogate endpoint in clinical trials for chronic kidney disease, with potential to enable detection of events earlier in the disease course.

Exome sequencing of patients with congenital heart disease (CHD) and their unaffected parents reveals an excess of strong-effect, protein-altering de novo mutations in genes expressed in the developing heart, many of which regulate chromatin modification in key developmental genes; collectively, these mutations are predicted to account for approximately 10% of severe CHD cases.