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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.

This cross-sectional study in two independent middle-aged and aged cohorts investigates whether psychological characteristics associated with varying dementia risk aggregate into psychological profiles and relate to aging brain health.

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.

Here the authors identify TNIP1 as a risk factor for a fatal neurodegenerative disorder and discover specific genetic loci associated with the three main subtypes of this disorder. The findings highlight distinct disease mechanisms, emphasizing the roles of immunity and the notch signaling pathway.

Here, the authors perform large trans-ancestry fine-mapping analyses identifying large numbers of association signals and putative target genes for colorectal cancer risk, advancing our understanding of the genetic and biological basis of this cancer.

GIANT, a genetically informed brain atlas, integrates genetic heritability with neuroanatomy. It shows strong neuroanatomical validity and surpasses traditional atlases in discovery power for brain imaging genomics.

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

The OX40-OX40L axis is a crucial component of the costimulatory requirement of CD4 T cell responses. Here, the authors show context and cell type specific expression of OX40L for driving Th1 cell generation during acute and chronic models of infection.

As low-carbon energy technologies advance, markets are driving demand for energy transition metals, increasing the stress placed on people and the environment in extractive locations. Here, the authors quantify this stress by developing a set of global composite environmental, social and governance risk indicators, and find that 84% of platinum resources and 70% of cobalt resources are located in high-risk contexts.

An increase in shigellosis cases among men who have sex with men in the United Kingdom has been linked to an extensively drug-resistant strain of Shigella sonnei. In this genomic epidemiology study, the authors investigate the genetic basis, evolutionary history, and international dissemination of the outbreak strain.

A national prospective study of patients requiring hospitalization for COVID-19 demonstrates global cognitive deficits at 1 year, associated with elevated brain injury markers and reduced gray matter volume.

COVID-19 can be associated with neurological complications. Here the authors show that markers of brain injury, but not immune markers, are elevated in the blood of patients with COVID-19 both early and months after SARS-CoV-2 infection, particularly in those with brain dysfunction or neurological diagnoses.

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.

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.

A multi-ancestry genome-wide association study meta-analysis, combined with transcriptome- and methylome-wide association analyses, identifies risk loci associated with colorectal cancer. Credible effector genes and their target tissues are also highlighted, showing that over a third probably act outside the colonic mucosa.

Nephrophthisis (NPH) is a common manifestation of ciliopathy diseases. Here the authors identify mutations in intraflagellar transport 54 (IFT54) in patients with NPH and discover an extra-ciliary role for IFT54 in regulating cytoplasmic microtubule dynamics, that contributes to the pathophysiology of this disease.

Escherichia albertii is an emerging gastrointestinal pathogen that causes disease in humans and animals, notably birds. In this genomic epidemiology study, the authors investigate characteristics of isolates sampled from humans and birds in Great Britain and find that they tend to cluster separately.

CD8⁺ T cell activation involves cooperation between the T cell receptor and the integrin LFA-1. Here authors show how LFA-1 nanoclusters participate in the calibration of TCR stimulation strength and activation of cytotoxic function in CD8⁺ T cells.

Shigella sonnei is one of the main species causing shigellosis worldwide. Here the authors analyse nearly 400 S. sonnei genome sequences and carry out experimental evolution experiments to shed light into the evolutionary processes underlying the recent emergence of fluoroquinolone resistance in this pathogen.

Richard Houlston and colleagues report a genome-wide association study for colorectal cancer. They report three loci newly associated with colorectal cancer, bringing the total number of common susceptibility loci to 20.

Whole genome sequencing is increasingly being adopted for Shigella sonnei outbreak investigation and surveillance, but there is no global classification standard. Here, the authors develop and validate a genomic framework implemented using open-source software, and demonstrate its application using surveillance data.

A transiting planet with a period of about 8.5 days and a radius 0.4 times that of Jupiter is reported within the debris disk around the star AU Microscopii.

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

Antimicrobial resistance (AMR) in Shigella species is a public health concern. Here, Baker et al. show how horizontal transfer of an AMR plasmid among Shigella species contributes to epidemics in men who have sex with men in England.

In colorectal cancer (CRC), finding loci associated with risk may give insight into disease aetiology. Here, the authors report a genome-wide association analysis in Europeans of 34,627 CRC cases and 71,379 controls, and find 31 new risk loci and 17 new risk SNPs at previously reported loci.

Primary ciliary dyskinesia (PCD) is a genetically heterogeneous disease resulting in reduced mucus clearance and impaired lung function. Here, the authors show that mutations in PIH1D3 are responsible for an X-linked form of PCD, affecting assembly of a subset of inner arm dyneins.

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.

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.

In this Review, Scott et al. review our current knowledge of Shigella sonnei, highlighting recent insights into this globally disseminated antimicrobial-resistant pathogen and assessing how novel data may have an impact on future vaccine development and implementation.

Global phylogenetic analyses of Shigella dysenteriae isolates uncover the transcontinental transmission events and evolution of antibiotic resistance behind the major dysentery epidemics in the modern era.

Detailed clinical and virologic characteristics of the first 12 individuals with COVID-19 in the United States from the US Centers for Disease Control and Prevention.