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Affinity-proteomics platforms often yield poorly correlated measurements. Here, the authors show that protein-altering variants drive a portion of inter-platform inconsistency and that accounting for genetic variants can improve concordance of protein measures and phenotypic associations across ancestries.

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

Liang et al. estimate the prevalence of text modified by large language models in recent scientific papers and preprints, finding widespread use (up to 17.5% of papers in computer science).

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.

GWAS have identified more than 500 genetic loci associated with blood lipid levels. Here, the authors report a genome-wide analysis of interactions between genetic markers and physical activity, and find that physical activity modifies the effects of four genetic loci on HDL or LDL cholesterol.

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.

A multi-ancestry genome-wide gene–smoking interaction study identifies 13 new loci associated with serum lipids.

Here, the authors implement a genetic approach grouping fasting insulin-associated genetic variants based on their genetic and phenotypic similarities and highlight specific processes that decouple increased fasting insulin levels from T2D and cardiovascular risk, offering potential avenues for investigating process-specific pathways of disease risk.

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.

Meta-analyses in up to 1.3 million individuals identify 87 rare-variant associations with blood pressure traits. On average, rare variants exhibit effects ~8 times larger than the mean effects of common variants and implicate candidate causal genes at associated regions.

Claudia Langenberg, James Meigs and colleagues apply a joint meta-analysis approach that accounts for differences in body mass index to identify variants associated with glycemic traits. They report six new loci associated with fasting insulin levels and provide insights into the genetic basis of insulin resistance.

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

Jayavelu, Samaha et al., apply machine learning models on hospital admission data, including antibody titers and viral load, to identify patients at high risk for Long COVID. Low antibody levels, high viral loads, chronic diseases, and female sex are key predictors, supporting early, targeted interventions.

IBS is a prevalent condition worldwide that incurs substantial health-care costs. The condition can be difficult to diagnose owing to is multifactorial aetiology. Here, the authors provide an overview of the current approaches available to diagnose IBS, including symptoms, symptom-based criteria, biomarkers and psychological markers. Future directions for the field are also discussed.

A multi-ancestry genome-wide association meta-analysis of kidney cancer identifies 63 regions associated with disease susceptibility including one locus that was associated with increased risk in individuals with African ancestry.

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.

The single-cell gene expression changes during spinal cord formation and neurogenesis in mice are unclear. Here, the authors use a HES5 reporter to live image, then mathematically model, oscillations in single cells in presumed progenitors and neurons of the developing spinal cord.

Our understanding of the functional link between differential DNA methylation and type 2 diabetes and obesity remains limited. Here the authors present a blood-based EWAS of fasting glucose and insulin among 4808 non-diabetic Europeans and identify nine CpGs not previously implicated in glucose, insulin homeostasis and diabetes.

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.

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.

Exome-sequencing analyses of a large cohort of patients with type 2 diabetes and control individuals without diabetes from five ancestries are used to identify gene-level associations of rare variants that are associated with type 2 diabetes.

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.

Sleep duration is associated with an adverse lipid profile. Here, the authors perform genome-wide gene-by-sleep interaction analysis and find 49 previously unreported lipid loci when considering short or long total sleep time.

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.

Exome sequencing and copy number analysis are used to define genomic aberrations in early sporadic pancreatic ductal adenocarcinoma; among the findings are mutations in genes involved in chromatin modification and DNA damage repair, and frequent and diverse somatic aberrations in genes known as embryonic regulators of axon guidance.

Patricia Munroe, Joanna Howson and colleagues genotype ∼350,000 individuals and identify 30 new blood pressure– or hypertension-associated risk loci. Their analyses provide insights into the pathophysiology of hypertension and highlight new potential targets for clinical intervention.

A transancestral exome-wide association study for body-fat distribution identifies protein-coding variants that are significantly associated with waist-to-hip ratio adjusted for body mass index.

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.

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.

Solid organ transplant recipients are at increased risk of infectious disease and have unique molecular pathophysiology. Here the authors use host-microbe profiling to assess SARS-CoV-2 infection and immunity in solid organ transplant recipients, showing enhanced viral abundance, impaired clearance, and increased expression of innate immunity genes.

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.

Vaccination is effective in protecting from COVID-19. Here the authors report immune responses and breakthrough infections in twice-vaccinated patients receiving anti-TNF treatments for inflammatory bowel disease, and find dampened vaccine responses that implicate the need of adapted vaccination schedules for these patients.

This report by the Consortium for Refractive Error and Myopia uses gene-environment-wide interaction study (GEWIS) to identify genetic loci that affect environmental influence in myopia development, and identifies ethnic specific genetic loci that attribute to eye refractive errors.