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Understanding the underlying pathophysiology of obesity can help prevent this condition. Here, the authors perform a GWAS of BMI in diverse ancestries, finding four missense variants in FRS3 that affect BMI.

Genome-wide association analyses identify new risk loci for heart failure and its subtypes, extending understanding of the underlying biological pathways and disease mechanisms.

Oncolytic viruses are a promising therapeutic approach for cancer treatment. The authors demonstrate the efficacy of an engineered HSV-1 expressing PTENα as an oncolytic and immune stimulating therapy against brain cancer metastases.

Genome-wide association analyses comprising 14,256 cases and 1,199,156 controls and incorporating correlated cardiac magnetic resonance imaging traits provide insights into the molecular etiology of dilated cardiomyopathy.

Ostrowski and colleagues identify a tumour-suppressive pathway in the tumour stroma. They show that PTEN loss in stromal fibroblasts downregulates miR-320, leading to the upregulation of the ETS2 transcription factor and the induction of a secretome that promotes tumour growth, invasion and angiogenesis.

A genome-wide study by the Long COVID Host Genetics Initiative identifies an association between the FOXP4 locus and long COVID, implicating altered lung function in its pathophysiology.

Cancer-associated fibroblasts (CAFs) are the main component of the stroma in pancreatic cancer, but their tissue of origin remains to be defined. Here the authors perform lineage tracing and single cell RNA sequencing in mice and suggest the splanchnic mesenchyme as the tissue of origin for CAFs.

The tumour microenvironment has an important role in tumorigenesis. Here, the genetic inactivation of Pten in stromal fibroblasts of mouse mammary glands is shown to accelerate the initiation, progression and malignant transformation of mammary epithelial tumours. The data presented suggest that the Pten–Ets2 axis — Ets2 being a transcription factor activated by the loss of Pten — is a critical stroma-specific signalling pathway that suppresses mammary epithelial tumours.

A genome-wide association study meta-analysis combined with multiomics data of osteoarthritis identifies 700 effector genes as well as biological processes with a convergent involvement of multiple effector genes; 10% of these genes express the target of approved drugs.

Genome-wide association meta-analysis of AAA identifies 121 independent risk loci and highlights potential therapeutic targets such as proprotein convertase, subtilisin/kexin-type 9 (PCSK9).

Genome-wide association meta-analyses identify more than 350 loci associated with atrial fibrillation. A polygenic score derived from these results improves atrial fibrillation risk prediction compared to published clinical and polygenic scores.

The galectin family of secreted lectins are important regulators of immune cell function; however, their role in B cell responses is poorly understood. Here, the authors identify IgM-BCR as a ligand for galectin-9. In resting naive cells, they show that galectin-9 mediates a close association between IgM and CD22.

Genome-wide analyses using fetal and parental genotypes identify 40 independent associations influencing placental weight and highlight the role of the fetus in preeclampsia risk and placental growth regulation via insulin signaling.

Our current understanding of cilia biology and ciliary diseases is incomplete, in part because cilia are hard to visualize. Here, the authors use cryo-electron tomography to image the structure of human cilia with high resolution and uncover the elusive ciliary defects in Primary Ciliary Dyskinesia patients.

HIV infection over time is thought to result in premature aging and aberrant immune responses including the induction of immunological senescence. Here the authors show altered formation of immune synapses by naive CD8⁺ T cells and dysregulated synapse functioning at late differentiated stages in people living with HIV.

Although co-occurring species may differ widely in their response traits, coordinated functional trait shifts may emerge at the community level in response to environmental factors. Here, the authors use data from 150 grassland sites to identify a coordinated slow-fast strategy response to land-use intensification across above- and belowground taxa.

The human gut microbiota can metabolize xanthan gum, a food additive that was introduced to our diets relatively recently in processed foods. A Ruminococcaceae species can degrade this complex polysaccharide and, in some individuals, Bacteroides intestinalis can grow on the released oligosaccharide products.

RNA polymerase II has an unexpected function in the nucleolus, helping to drive the expression of ribosomal RNA and to protect nucleolar structure through a mechanism involving triplex R-loop structures.

Little is known about the biology of back pain, a leading cause of disability. Here the authors report 30 new back pain loci, implicating genes involved in cartilage/bone biology, as well as neurological and inflammatory processes.

Arginine methylation has been reported to regulate AKT-associated signalling. Here, the authors show that PRMT5-mediated arginine methylation promotes AKT activity and induces tumourigenesis.

People with Down's syndrome seem to have a decreased incidence of solid tumours. This paper reports a mouse model for intestinal tumours in which trisomy for a subset of mouse orthologues of chromosome 21 genes reduces tumour incidence, whereas monosomy of the same genes increases the number of tumours. This dosage-dependent effect can to a large extent be attributed to the transcription factor Ets2.

Serological tests are important diagnostic and disease surveillance tools for addressing the COVID-19 pandemic. Here, the authors present a tri-part Nanoluciferase based assay to detect antibodies against SARS-CoV-2.

A multi-ancestry genome-wide association study of liver cirrhosis and its associated endophenotypes identifies and validates 14 risk variants. Integrative common and rare variant analyses provide insights into the genetic architecture of liver cirrhosis.

Genome-wide association analyses of migraine and its subtypes identify new susceptibility loci, including rare variants with large effects implicating PRRT2, SCN11A and KCNK5.

Genome-wide analyses identify loci associated with nonalcoholic fatty liver disease, including rare, protective loss-of-function variants in MTARC1 and GPAM. Plasma proteomic analyses provide insight into proteins involved in disease pathogenesis.

Interferon (IFN) is an important component of antiviral immunity, but can also be exploited by bacteria for immune evasion. Here the authors show that Listeria monocytogenes (Lm) induces type I IFN to suppress the degradation of Lm virulence proteins, ActA and LLO, and promote Lm infection in an IFITM3-dependent manner, thereby hinting at a potential target for antimicrobial therapy.

The underlying genetics of carpal tunnel syndrome is not well understood. Here, the authors perform a GWAS meta-analysis for carpal tunnel syndrome finding variants at 50 loci with connections to the extracellular matrix discovered through various functional analyses.

The authors test whether spatial scale (plot, local and landscape) affects the supply of various ecosystem services in grasslands, finding that some services are predicted by plot-level properties while others depend more on landscape-level management.

In situ vaccine recruits and activates cross-presenting dendritic cells and augments PD1 blockade efficacy in patients with indolent non-Hodgkin’s lymphoma.

Epithelial to mesenchymal transition (EMT) is a fundamental process in both development and cancer progression. The transcription factor Elf5 is now reported as an upstream regulator of the key EMT inducer Snail2, and is shown to regulate the earliest known rewiring events required for tumour cell invasiveness and metastasis.

Managing landscapes sustainably is challenging given the competing interests of different stakeholder groups. By combining broad ecological data with information on the ecosystem service priorities of multiple stakeholder groups, this study provides a tool to quantify the social impact of land-use changes.

The tumor microenvironment influences tumor progression. Here the authors show that lack of stromal PTEN phosphatase induces DNA repair defects in the neighboring mammary gland epithelial cells via hyperactivation of EGF-receptor signaling, resulting in higher radiation-induced DNA damage and hyperplasia.

Land use intensification is a major driver of biodiversity change. Here the authors measure diversity across multiple trophic levels in agricultural grassland landscapes of varying management, finding decoupled responses of above- and belowground taxa to local factors and a strong impact of landscape-level land use.

CEACAM1 functions as a novel heterophilic ligand for TIM-3 and is necessary for TIM-3-mediated tolerance, which has marked consequences for inflammation, infection and cancer.

Initially identified more than 30 years ago, the ETS family of transcription factors has been found to take part in all steps of tumorigenesis. This Review discusses the different mechanisms of ETS activation and the oncogenic implications of this activation, as well as how to target ETS factors in cancer treatment.

The largest meta-analysis of GWASs of hepcidin and sTfR identified 43 genomic loci, of which 15 new. Mendelian randomisation revealed associations of systemic iron status and iron-related loci with selected health outcomes across multiple domains.