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

A cross-ancestry meta-analysis of genome-wide association studies identifies association signals for stroke and its subtypes at 89 (61 new) independent loci, reveals putative causal genes, highlighting F11, KLKB1, PROC, GP1BA, LAMC2 and VCAM1 as potential drug targets, and provides cross-ancestry integrative risk prediction.

The identification of T cell epitopes is a critical step in understanding the immune response to infection and in designing vaccine based approaches. Here the authors introduce a frame work of antigen discovery called MHCvalidator and Epitrack to identify new antigenic features for T-cell COVID-19 vaccines and characterise a novel non-canonical epitope from a truncated Spike variant and mutation of an immunodominant epitope in the BNT162b4 vaccine.

In a post-approval study including more than 17,000 patients on the safety of pulsed field ablation, a new method for treatment of atrial fibrillation, the procedure was found to have a low rate of adverse events but was associated with some unexpected rare complications that will need further study.

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.

Cohort-scale integration of clinical and proteomic data from tumor tissues in patients with pancreatic ductal adenocarcinoma led to the identification of a prognostic risk model for patient stratification as well as biomarkers of response to adjuvant chemotherapy, validated in independent external cohorts.

Richard Duerr and colleagues present a genome-wide association study of ulcerative colitis. They identify new risk loci on chromosomes 1p36 and 12q15.

SARS-CoV-2 variant Omicron has been suggested to cause less severe disease. This prospective study shows that the clinical phenotype in patients infected with Omicron differs from patients infected with Delta but no association between Delta and Omicron including sublineages and mortality was observed.

Tougeron et al. evaluate the prognostic value of circulating tumor DNA (ctDNA) in predicting the efficacy of immune checkpoint inhibitors (ICI) plus chemotherapy in advanced gastric adenocarcinoma. An early decrease in ctDNA concentration is associated with a worse objective response rate, shorter progression free survival and overall survival.

Analyses of virological and surveillance data in France show that a substantial proportion of symptomatic cases of COVID-19 have remained undetected and that easily accessible and efficient testing is required to control the pandemic.

Rapid and effective molecular subtyping of pancreatic adenocarcinoma (PDAC) is important for prognosis and treatment. Here, the authors develop PACpAInt, a deep learning model for PDAC molecular subtyping from whole-slide histological imaging that enables the analysis of heterogeneity and prognostic predictions.

Genome-wide analysis of chronic obstructive pulmonary disease identifies 82 loci, 35 of which are new. Integration of gene expression and genomic annotation data shows enrichment of signals in lung tissue, smooth muscle and several lung cell types.

Gastrointestinal stromal tumors can respond to imatinib mesylate therapy owing to its inhibitory action on tumor cells as well as off-target effects on NK cells. This report shows that a different frequency of genetically determined expression profiles of isoforms of the NK cell receptor NKp30, which show various functional properties, is associated with GIST and influences survival after imatinib treatment.

Suppressive combination antiretroviral therapy fails to eradicate HIV-1 latent reservoirs in poorly characterized cell compartments. Here, urethral macrophages, but not urethral T cells, are shown to contain integrated HIV-1 DNA and to be able to release infectious HIV-1 following reactivation with lipopolysaccharide.

In patients with colorectal cancer, resection of liver-limited metastatic disease provides the only chance of cure. A recent study showed that the addition of cetuximab to conventional chemotherapy significantly increased the response rate and the rate of liver metastases resection in patients with colorectal cancer, providing another chance to cure patients with initially liver-limited unresectable disease.

The association between blood pressure (BP) and migraine is poorly understood. Here, the authors explore this relationship using summary-level GWAS data for BP and migraine. Cross-trait meta-analysis reveals shared loci between BP and migraine, while Mendelian randomization suggests that diastolic BP specifically plays a key role in migraine susceptibility.

Respiratory syncytial virus (RSV) causes severe respiratory disease in young children. Here, Rameix-Welti et al. create fluorescent and bioluminescent RSV strains that allow real-time analysis of viral replication and screening of antiviral compounds in cultured cells and in live animals.

Mark Caulfield, Paul Elliott and colleagues use data from the UK Biobank to perform genome-wide association analysis for blood pressure traits. They identify and validate 107 novel loci and highlight new biological pathways for potential therapeutic intervention for hypertension.

Symptomatic stenoses of arteriovenous hemodialysis fistulas can be treated with surgery or endovascular dilatation. Here, an interventional radiologist argues that the minimal invasiveness and better venous preservation associated with endovascular treatment more than offset the disadvantages of poor primary patency rates and high cost, regardless of whether the fistula is located in the upper or lower forearm. Specific contraindications to each approach are also highlighted.

Age-related bone loss can eventually result in osteoporosis. In this Review, Pierre Marie describes an emerging therapy that involves targeting certain integrin transmembrane proteins to promote the differentiation of mesenchymal stromal cells into osteoblasts, thereby counteracting bone loss.

Using whole-genome data for single-nucleotide polymorphism and results from genome-wide association studies, the authors show that people’s preference for pairing with those with similar phenotypic traits has genetic causes and consequences.

John Rioux and colleagues report results of a large genome-wide association meta-analysis and follow-up study of ulcerative colitis. They identify 29 new risk loci for this inflammatory disease and show that many risk loci are shared between ulcerative colitis and Crohn's disease.

Chromatin and transcriptome studies in myelomonocytic leukemia stem cells revealed repression of retroelements and immune genes. Restoring these pathways by co-inhibiting DNA methylation and H3K9me2 enables selective targeting of leukemic cells.

Hyperphosphataemia is associated with poor clinical outcomes but strong evidence that targeting serum phosphate improves these outcomes is lacking. Here the authors discuss the role, regulation and management of serum phosphate in chronic kidney disease, including the efficacies of phosphate binder therapy and dietary interventions.