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cellSTAAR advances noncoding rare variant association analysis by integrating single-cell genomics data.

China’s crowded coasts must balance seafood demand with conserving migratory shorebirds that rely on tidal flats along the East Asian–Australasian Flyway. This study suggests that well-managed mariculture feeds shorebirds and limits overharvest, benefiting seafood production and biodiversity.

Parkinson’s disease (PD) is a common neurodegenerative disorder with a complex etiology involving genetics and the environment. Here, Vallerga et al. identify two CpG probes associated with PD in a blood cell type-corrected epigenome-wide meta-analysis, implicating the SLC7A11 gene as a plausible biological target.

Spatial transcriptomic analysis of cells in intestinal fistulae of patients with Crohn’s disease reveals the existence of specialized fistula-associated cell states with distinct signalling profiles and extracellular matrix architecture.

Analysis of copy number alterations in 1,451 patient-derived xenografts (PDXs) and matched patient tumor samples shows strong conservation from patient tumors through late-passage PDXs and a lack of systematic copy number evolution driven by the mouse host.

MultiSTAAR provides a general and flexible statistical framework for functionally informed multi-trait rare variant analysis of biobank-scale sequencing studies by jointly analyzing multiple traits and incorporating annotation information.

Analyses of genome and exome sequencing data identify rare coding and structural variants associated with atrial fibrillation and highlight genetic links between atrial fibrillation and cardiomyopathies.

Parkinson’s disease (PD) features visual dysfunction. Here the authors show mice lacking VPS35, a retromer component genetically linked to PD, in rods have impaired vision, retinal degradation and a-synuclein inclusions.

Large genome-wide meta-analysis of clinically diagnosed late-onset Alzheimer’s disease (LOAD) from 94,437 individuals identifies new LOAD risk loci and implicates Aβ formation, tau protein binding, immune response and lipid metabolism.

KRAS-driven cancers remain refractory to current clinical therapies. In this study, the authors show that lung and pancreatic cancers expressing oncogenic KRAS can be targeted by genetic inhibition of FOSL1, which involves downregulation of genes of the mitotic machinery.

As immune checkpoint therapy is more frequently used for cancer, side effects such as Stevens-Johson syndrome / toxic epidermal necrolysis (SJS/TEN) are becoming more common. Here the authors use single cell transcriptomics to implicate TNF and CXCL10 in recruitment of CXCR3⁺ cytotoxic T cell in SJS/TEN skin lesions.

Although the common genetic variants contributing to blood lipid levels have been studied, the contribution of rare variants is less understood. Here, the authors perform a rare coding and noncoding variant association study of blood lipid levels using whole genome sequencing data.

Using data from a single time point, passenger-approximated clonal expansion rate (PACER) estimates the fitness of common driver mutations that lead to clonal haematopoiesis and identifies TCL1A activation as a mediator of clonal expansion.

Meta-analysis of genome-wide association studies on Alzheimer’s disease and related dementias identifies new loci and enables generation of a new genetic risk score associated with the risk of future Alzheimer’s disease and dementia.

The first real quantum-mechanical computations have now been made. But current techniques cannot be scaled up to produce useful quantum computers. A radical scheme, using semiconductor physics to manipulate nuclear spins, could be the answer.

There are currently no licensed vaccines to prevent Group A Streptococcus (GAS) infections. In this study, the authors evaluate the immune response and preclinical efficacy of a multicomponent mRNA lipid-nanoparticle vaccine against GAS.

A meta-analysis of genome-wide association studies of type 2 diabetes (T2D) identifies more than 600 T2D-associated loci; integrating physiological trait and single-cell chromatin accessibility data at these loci sheds light on heterogeneity within the T2D phenotype.

Here the authors present a large genetic study in East Asians that identifies 97 genetic regions linked to kidney function. These findings aim at better understanding chronic kidney disease in diverse populations.

Pooling participant-level genetic data into a single analysis can result in variance stratification, reducing statistical performance. Here, the authors develop variant-specific inflation factors to assess variance stratification and apply this to pooled individual-level data from whole genome sequencing.

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.

STAARpipeline is a comprehensive framework for flexible and scalable rare-variant association analysis using whole-genome sequencing data and annotation information.

In Alzheimer’s disease (AD) tau and neurodegeneration have complex regional relationships. Here, the authors show neuronal hypometabolism discordant with tau burden defines functional resilience or susceptibility to Alzheimer’s pathology via limbic/cortical axes. Susceptible groups have faster cognitive decline and evidence of non-Alzheimer’s pathologies.

The way you were taught quantum mechanics depends on when you were a student; pedagogical approaches over the last century have been driven by social and political trends. Physicist and historian, David Kaiser, charts how the emphasis of quantum education has oscillated between philosophy and practicality.

The goals, resources and design of the NHLBI Trans-Omics for Precision Medicine (TOPMed) programme are described, and analyses of rare variants detected in the first 53,831 samples provide insights into mutational processes and recent human evolutionary history.

This study finds that sST2 is a disease-causing factor for Alzheimer’s disease. Higher sST2 levels impair microglial Aβ clearance in APOE4⁺ female individuals. A genetic variant, rs1921622, is associated with a reduction in sST2 level and protects against AD in APOE4⁺ female individuals.

The influence of X chromosome genetic variation on blood lipids and coronary heart disease (CHD) is not well understood. Here, the authors analyse X chromosome sequencing data across 65,322 multi-ancestry individuals, identifying associations of the Xq23 locus with lipid changes and reduced risk of CHD and diabetes mellitus.

Andrew Morris, Mark McCarthy, Michael Boehnke and colleagues report a meta-analysis of genome-wide association studies for type 2 diabetes, including 26,488 cases and 83,964 controls from populations of European, east Asian, south Asian and Mexican and Mexican American ancestry. They identify seven loci newly associated with type 2 diabetes and examine the genetic architecture of disease across populations.

Analysis of 97,691 high-coverage human blood DNA-derived whole-genome sequences enabled simultaneous identification of germline and somatic mutations that predispose individuals to clonal expansion of haematopoietic stem cells, indicating that both inherited and acquired mutations are linked to age-related cancers and coronary heart disease.

A study shows that clonal haematopoiesis of indeterminate potential is associated with an increased risk of chronic liver disease specifically through the promotion of liver inflammation and injury.

Platelet aggregation is associated with myocardial infarction and stroke. Here, the authors have conducted a whole genome sequencing association study on platelet aggregation, discovering a locus in RGS18, where enhancer assays suggest an effect on activity of haematopoeitic lineage transcription factors.

Most studies of the genetics of the metabolome have been done in individuals of European descent. Here, the authors integrate genomics and metabolomics in Black individuals, highlighting the value of whole genome sequencing in diverse populations and linking circulating metabolites to human disease.

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 multi-ancestry transcriptome-wide association study using an optimal linear combination of association statistics provides insights into tobacco use biology and suggests opportunities for drug repurposing.

Genome-wide association and fine-mapping analyses in ancestrally diverse populations implicate candidate causal genes and mechanisms underlying type 2 diabetes. Trans-ancestry genetic risk scores enhance transferability across populations.

Progressive diseases tend to be heterogeneous in their underlying aetiology mechanism, disease manifestation, and disease time course. Here, Young and colleagues devise a computational method to account for both phenotypic heterogeneity and temporal heterogeneity, and demonstrate it using two neurodegenerative disease cohorts.

In this study the authors identify a possible link between the gene FAM222A and brain atrophy. The protein it encodes is found to accumulate in plaques seen in Alzheimer’s disease, and functional analysis suggests it interacts with amyloid-beta.

Identification of disease modules in the human interactome can guide more efficacious therapeutic selections. Here, the authors introduce a network-based methodology to identify individualized disease modules by mapping patients’ DNA and RNA sequencing profiles to the interactome, enabling prediction of cancer type-specific drug responses.

The GLASS Consortium studies the evolutionary trajectories of 222 patients with a diffuse glioma to aid in our understanding of tumour progression and treatment failure

This Review discusses multiomic approaches for the characterization and biological understanding of cellular senescence, including detailed case studies on skeletal muscle and adipose tissue that highlight current outstanding issues in the field.

Structural variants (SVs) in human genomes contribute diversity and diseases. Here, the authors use a multi-platform strategy to generate haplotype-resolved SVs for three human parent–child trios.

Genetic variation in ANGPTL4 is associated with lipid traits. Here, the authors find that predicted loss-of-function variants in ANGPTL4 are associated with glucose homeostasis and reduced risk of type 2 diabetes and that Angptl4^−/− mice on a high-fat diet show improved insulin sensitivity.

Alzheimer’s disease is heterogeneous in its neuroimaging and clinical phenotypes. Here the authors present a semi-supervised deep learning method, Smile-GAN, to show four neurodegenerative patterns and two progression pathways providing prognostic and clinical information.