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Analysis of whole-genome sequences of 25,465 individuals of European ancestry shows that rare variants contribute substantially to the heritability of height and body mass index.

A combination of large-scale phylogenomic analysis, mouse lethality experiments and bacterial growth assays shows that gene loss in the putrescine utilization pathway has enhanced biofilm formation and transmission-related characteristics in the pandemic clone of a bacterial pathogen, Vibrio parahaemolyticus, promoting successive waves of global transmission events.

This Primer by Wilson and colleagues summarizes the epidemiology, pathophysiology, diagnosis and treatment of neurological and psychiatric manifestations of COVID-19.

A meta-analysis of genome-wide association studies across different populations highlights new risk loci and provides a genetic risk score that can stratify prostate cancer risk across ancestries.

A long-range MYC enhancer is duplicated in human T-ALL and is required for T cell development and NOTCH1-induced leukemogenesis.

MetaSTAAR enables functionally informed rare variant association analysis in biobank-scale cohorts using an efficient, sparse matrix approach for summary statistic storage.

In a phase 1 trial of patients with advanced systemic mastocytosis, avapritinib, a selective KIT inhibitor, was generally well tolerated, elicited durable clinical responses and led to reductions in mast cell disease burden.

Using multi-ancestry genome-wide association study and fine-mapping, 298 loci and 36 credible genes are identified in the aetiology of bipolar disorder.

Efficient electro-optic conversion is central to photonic computing, and thin-film lithium niobate (TFLN) offers this capability. Here, the authors demonstrate computing circuits on the TFLN platform, enabling the next generation of photonic computing systems featuring both high-speed and low-power.

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.

Notch signalling modulates fate decisions in stem and progenitor cells in various tissues. Artavanis-Tsakonas and colleagues use in vivo genetic labelling to uncover cell progenitors that are implicated in mammary gland branching and alveolar formation.

Inhibition of cyclooxygenase 1 releases T cells from immunosuppression by platelet-derived thromboxane A₂, thereby enhancing the immune response against metastasis.

Analysis of mitochondrial genomes (mtDNA) by using whole-genome sequencing data from 2,658 cancer samples across 38 cancer types identifies hypermutated mtDNA cases, frequent somatic nuclear transfer of mtDNA and high variability of mtDNA copy number in many cancers.

Efficient, large-scale genomic analysis is facilitated on the cloud by a computational tool with error-diagnosing and self-healing capabilities.

Whether multimorbidity accelerates brain Aβ deposition in humans remains largely unknown. Here, the authors demonstrate that higher self-reported multimorbidity burden predicts increased brain Aβ accumulation rates in the ADNI cohort.

The role of orbital degrees of freedom in determining the electronic structure remains obscured. Here, Walkup et al. report strain-induced band structure changes in a topological crystalline insulator SnTe, whose surprising behavior reflects the  orbital nature of bands.

A series of early-time, multiwavelength observations of an optical transient, AT2022cmc, indicate that it is a relativistic jet from a tidal disruption event originating from a supermassive black hole.

A sequencing chemistry that separates nucleotide identification from nucleotide incorporation achieves high accuracy.

Exome-wide analysis identifies rare and low-frequency coding variants associated with body mass index. Gene-based meta-analysis and functional studies implicate 13 genes, eight of which are novel, and neuronal pathways as factors in human obesity.

Broadly neutralizing antibodies (bnAbs) for HIV have been difficult to elicit with one issue being the low B cell affinity required. Here the authors use a transgenic mouse bearing human-like antibody repertoires to show that low affinity B cells persist which enables vaccine expansion of antibodies against the CD4 binding site, a conserved HIV bnAb target.

Prostate cancer (PrCa) involves a large heritable genetic component. Here, the authors perform multivariate fine-mapping of known PrCa GWAS loci, identifying variants enriched for biological function, explaining more familial relative risk, and with potential application in clinical risk profiling.

Profiling RNA modifications is essential to understanding their functions. Here, authors present DirectRM, a nanopore sequencing analytical tool that simultaneously detects six RNA modifications, revealing that modifications cluster at the transcript level but exclude each other on individual RNA molecules.

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

Trans-ancestry meta-analysis of estimated glomerular filtration rate (eGFR) from 1,046,070 individuals identifies 264 associated loci, providing a resource of molecular targets for translational research of chronic kidney disease.

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

The authors summarize the data produced by phase III of the Encyclopedia of DNA Elements (ENCODE) project, a resource for better understanding of the human and mouse genomes.

A multi-ancestry genome-wide association study for age at menarche followed by fine mapping and downstream analysis implicates 665 pubertal timing genes, such as the G-protein-coupled receptor 83 (GPR83) and other genes expressed in the ovaries involved in the DNA damage response.

The genetics and clinical consequences of resting heart rate (RHR) remain incompletely understood. Here, the authors discover new genetic variants associated with RHR and find that higher genetically predicted RHR decreases risk of atrial fibrillation and ischemic stroke.

Samples of different body regions from hundreds of human donors are used to study how genetic variation influences gene expression levels in 44 disease-relevant tissues.

The study reveals the cryo-EM structure of human MICAL1, an enzyme that depolymerizes F-actin. Structural analyses show a conserved autoinhibition mechanism through intramolecular interactions between the N-terminal and C-terminal domains.

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.

John Chambers, Jaspal Kooner, Pim van der Harst, Shyong Tai, Paul Elliott, Jiang He, Norihiro Kato and colleagues performed a genome-wide association study of blood pressure phenotypes in individuals of European, East Asian and South Asian ancestry. They find trait-associated SNPs at 12 loci, some of which are associated with methylation at nearby CpG sites.

The increasing accessibility of single cell omics technologies beyond transcriptomics demands parallel advances in analysis. Here, the authors introduce STREAM, a pipeline for reconstruction and visualization of differentiation trajectories from both single-cell RNA-seq and ATAC-seq data.

A trans-ancestry meta-analysis of GWAS of glycemic traits in up to 281,416 individuals identifies 99 novel loci, of which one quarter was found due to the multi-ancestry approach, which also improves fine-mapping of credible variant sets.

A comprehensive analysis of the cell-specific molecular regulatory mechanisms underlying post-traumatic stress disorder in the human prefrontal cortex.

Arginylation is a post-translational modification that is difficult to distinguish from arginine residues using mass spectrometry. Now a method has been developed to profile protein arginylation ex vivo and is tested on different samples, revealing 235 unique arginylation sites in the human proteomes.

Hundreds of genetic loci associated with age at menopause, combined with experimental evidence in mice, highlight mechanisms of reproductive ageing across the lifespan.

Genome-wide analyses identify variants associated with sinus node dysfunction, distal conduction disease and pacemaker implantation, implicating ion channel function, cardiac developmental programs and sarcomeric structure in bradyarrhythmia susceptibility.

Several factors contribute to the identity of adipose stem cells, including anatomic location, microvascular neighborhood and sex. Here, authors find that adipose stem cells are sexual dimorphic cells with dual roles as preadipocytes and fibroblasts.

Transcriptomic and metabolic profiling reveals that the creatine kinase pathway is essential for growth of acute myeloid leukemias expressing the transcription factor EVI1.

A soft mesh microelectrode array can seamlessly integrate in developing brains, enabling long-term, stable mapping of how single-neuron activity and population dynamics emerge and evolve during brain development.

Gene fusions involving MLL and different partner genes define unique subgroups of acute myelogenous leukemia, but the mechanisms underlying specific subgroups are not fully clear. Here the authors elucidate the mechanisms of MLL-AF6 induced transformation, providing a distinct pathway that involves SHARP1 as a critical target.