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Similarities in cancers can be studied to interrogate their etiology. Here, the authors use genome-wide association study summary statistics from six cancer types based on 296,215 cases and 301,319 controls of European ancestry, showing that solid tumours arising from different tissues share a degree of common germline genetic basis.

Identifying jets originating from heavy quarks plays a fundamental role in hadronic collider experiments. In this work, the ATLAS Collaboration describes and tests a transformer-based neural network architecture for jet flavour tagging based on low-level input and physics-inspired constraints.

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.

Variants in NOS1AP can cause monogenic nephrotic syndrome. Here, the authors show that disrupting the intergenic NOS1AP splice isoform that is more prevalent in podocytes leads to monogenic kidney disease responsive to RAAS inhibition.

A study of several longitudinal birth cohorts and cross-sectional cohorts finds only moderate overlap in genetic variants between autism that is diagnosed earlier and that diagnosed later, so they may represent aetiologically different conditions.

New study shows that up to 50% of properties flooded after hurricane Harvey flooded because of climate change, with low-income and Latina/x/o neighborhoods experiencing higher climate change-attributed impacts.

Risk for renal cell carcinoma (RCC) is higher when there are first-degree family members with the disease. Here, Scelo and colleagues perform a genome-wide association meta-analysis and new genome-wide scan to identify seven new loci with significant RCC association.

Multi-ancestry genome-wide analyses identify 95 loci associated with post-traumatic stress disorder and implicate candidate genes, pathways and neurobiological systems underlying its pathophysiology.

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

Genome-wide analysis identifies 32 loci associated with breast cancer susceptibility, accounting for estrogen receptor, progesterone receptor and human epidermal growth factor receptor 2 status and tumor grade.

It is unclear how often genetic mosaicism of chromosome X arises. Here, the authors examine women with cancer and cancer-free controls and show that X chromosome mosaicism occurs more frequently than on autosomes, especially on the inactive X chromosome, but is not linked to non-haematologic cancer risk

Luis Pérez-Jurado, Stephen Chanock and colleagues detect clonal chromosomal abnormalities in peripheral blood or buccal samples from individuals in the general population. They show that the frequency of such events increases with age and is associated with elevated risk of developing subsequent hematological cancers.

Study shows PTSD predisposition shares distinct genes and genomic regions with several cardiovascular conditions. Here the findings reveal neuronal, immune, and metabolic pathways, and repurposed drug targets that further the understanding of the comorbidity.

Parasites such as malaria elicit an immune response in their host, causing cytokine levels to increase. In this study, a parasite housekeeping gene, tyrosyl-tRNA synthetase, is shown to bind to host macrophages and, once inside the cells, enhance the levels of proinflammatory cytokines.

By integrating healthcare and exome-sequencing data from parent–offspring trios of patients with developmental disorders, 28 genes that had not previously been associated with developmental disorders were identified.

Prostate cancer often does not progress to invasive disease and thus markers predicting the course of the disease progression are critical for optimal treatment choices. Here the authors show that variants at two genetic loci correlate with the aggressiveness of prostate cancer.

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.

Gene expression, alternative splicing and DNA methylation profiles from human kidney samples provide insights into the effects of common variants influencing blood pressure. Mendelian randomization uncovers the effects of blood pressure on renal outcomes.

The human endometrium repeatedly undergoes specific cyclic changes to prepare for embryo implantation. Understanding the mechanisms involved in endometrial cycling is important for the treatment of reproductive pathologies, and can also provide insight into conditions such as wound healing and even cancer.

Few therapeutic options are currently available for patients with glioblastoma, which are associated with a poor prognosis. Therapies with monoclonal antibodies, alone or linked to cytotoxic payloads, are currently being explored in these patients. Herein, the authors summarize therapeutic strategies based on antibody–drug conjugates (ADCs), targeted against EGFR, and discuss key aspects such as the blood–brain barrier, resistance mechanisms, and the development of specific biomarkers.

Susan Slager and colleagues report a meta-analysis of genome-wide association studies for chronic lymphocytic leukemia (CLL). They identify nine loci newly associated with CLL.

Developmental disorders (DDs) are more prevalent in males, thought to be due to X-linked genetic variation. Here, the authors investigate the burden of X-linked coding variants in 11,044 DD patients, showing that this contributes to ~6% of both male and female cases and therefore does not solely explain male bias in DDs.

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.

Merlini, Rafalski et al. show that dynamic microglial brain surveillance prevents hyperexcitability and seizures by G_i-dependent microglia–neuron interactions in response to evoked neuronal activity to maintain physiological network synchronization.

Chromodomain Helicase DNA-binding (CHD) proteins have been implicated in neurodevelopmental processes. Here, the authors identify missense variants in CHD3 that disturb its chromatin remodeling activities and cause a neurodevelopmental disorder with macrocephaly and speech and language impairment.

James Cerhan and colleagues report genome-wide association and meta-analysis studies to identify genetic susceptibility loci for diffuse large B cell lymphoma. They identify four loci that influence genetic susceptibility to this B cell malignancy.

Whole-exome analysis of individuals with developmental disorders shows that de novo mutations can equally cause loss or altered protein function, but that most mutations causing altered protein function have not yet been described.

The astronomical event GW170817, detected in gravitational and electromagnetic waves, is used to determine the expansion rate of the Universe, which is consistent with and independent of existing measurements.

Peripheral artery disease (PAD) is undergoing a major epidemiological transition, with a rapid shift from high-income to low-income and middle-income countries. In this Review, Fowkes et al. describe the measurement of PAD in populations, as well as the worldwide prevalence, risk factors, and burden of the disease.

The increasing availability of sequencing has accelerated the discovery of genetic causes of kidney disease, with clear benefits for patients. However, insufficient or contradictory evidence exists for numerous variants that were previously reported to be pathogenic, calling into question some proposed gene–disease associations. Rigorous re-appraisal of evidence is needed to ensure diagnostic accuracy.

Meredith Yeager, Stephen Chanock and colleagues analyze mosaic loss of the Y chromosome in three prospective cohorts and observe association with age and smoking but not with cancer survival. They also identify common variation at TCL1A associated with increased risk of mosaic loss of the Y chromosome.

The catalogue of genetic factors that have been implicated in kidney disease continues to grow. In this guide to gene–disease relationships, the authors discuss the crucial process whereby genetic and experimental data are critically evaluated to determine whether a genetic variant has a role in kidney disease, which can affect patient diagnosis, prognosis and management.