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Coronary artery disease has several genetic risk factors. Here, the authors develop a model that combines germline and somatic genetic drivers to predict coronary artery disease risk, identifying high-risk individuals not detected by polygenic risk scores alone.

Understanding collective behaviour is an important aspect of managing the pandemic response. Here the authors show in a large global study that participants that reported identifying more strongly with their nation reported greater engagement in public health behaviours and support for public health policies in the context of the pandemic.

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

Influenza A viruses spread through contact, large and small respiratory droplets (aerosols), but the relative importance of these modes of transmission is unclear. Cowling et al. model data from community trials of face masks and hand hygiene and find that aerosol transmission accounts for half of influenza occurrences.

How cells adapt to glucose starvation is still elusive. Here, Levy et al. show that the mTOR substrate 4EBP1 protects human, mouse, and yeast cells from glucose starvation and is exploited by cancer cells to promote tumorigenesis.

Here, the authors perform metagenomic analysis of Ecuadorian mothers and children showing that improved WASH and reduced animal exposure can lower antimicrobial resistance in the gut but may reduce gut microbial diversity, with the strongest effects observed in mothers.

Genomic studies of attention-deficit/hyperactivity disorder (ADHD) have advanced the understanding of its neurobiology but are still constrained by one of the most pronounced Eurocentric biases in psychiatric genetics. Expanding ADHD genomics to under-represented populations, particularly in Latin America, offers a unique opportunity to yield transformative discoveries by capturing the genetic diversity of admixed individuals. We call for a global, coordinated effort to prioritize diversity in ADHD research, not only to foster innovation in precision psychiatry but also to ensure that these advancements benefit all populations equitably.

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.

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.

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 advantage of living in cities compared with rural areas with respect to height and BMI in children and adolescents has generally become smaller globally from 1990 to 2020, except in sub-Saharan Africa.

Due to their small size, atomic-scale Josephson junctions are vulnerable to thermal fluctuations. Escribano et al. show that introducing a delayed feedback element, a common method to mitigate thermal noise, induces spontaneous oscillations that enhance capabilities of Josephson microscopy.

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.

What is the state of trust in scientists around the world? To answer this question, the authors surveyed 71,922 respondents in 68 countries and found that trust in scientists is moderately high.

Muñoz-Gil and colleagues report the results of an open challenge where they benchmarked algorithms for the characterization of motion changes in single-particle tracking. By ranking methods on simulations, the competition revealed strengths and limitations of AI and classic approaches, guiding researchers toward optimal tools.

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.

Vaccination with multiple doses has been proven effective against severe COVID-19, but protection levels widely vary among individuals. This study examines the serological and immunological profiles in recipients of multiple doses of Pfizer BNT162b2 vaccine for immune markers that correlate with protection against and susceptibility for SARS-CoV-2 infection.

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.

Respiratory syncytial virus is a major pathogen with burden observed and associated with childhood infection. Here the authors characterise a cationic adjuvant formulation and show single immunisation results in protection in a murine neonate model of respiratory syncytial virus infection.

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.

Here, the authors present results of the ZiBRA-2 project (https://www.zibra2project.org) which is an arbovirus surveillance project, across the Midwest of Brazil using a mobile genomics laboratory, combined with a genomic surveillance training program that targeted post-graduate students, laboratory technicians, and health practitioners in universities and laboratories.

Results for the final phase of the 1000 Genomes Project are presented including whole-genome sequencing, targeted exome sequencing, and genotyping on high-density SNP arrays for 2,504 individuals across 26 populations, providing a global reference data set to support biomedical genetics.

Literature produced inconsistent findings regarding the links between extreme weather events and climate policy support across regions, populations and events. This global study offers a holistic assessment of these relationships and highlights the role of subjective attribution.

This Registered Report presents evidence from 87 countries and regions showing that brief emotion-regulation interventions consistently reduced negative emotions and increased positive emotions during the COVID-19 pandemic.

This megastudy testing different interventions finds that honesty oaths are effective and can mitigate tax evasion in an incentivized game.

Analysis of HbA1c and FPG levels across 117 population-based studies demonstrates regional variation in prevalence of previously undiagnosed screen-detected diabetes using one or both measures and suggests that use of elevated FPG alone could underestimate diabetes prevalence in low- and middle-income countries.

Longitudinal multi-omics reveals shifts to the human microbiome across multiple body sites and the associated immune responses during short-term spaceflight.

An integrated data and sample repository for clinical, cellular and multi-omics research from diverse spaceflight missions known as Space Omics and Medical Atlas (SOMA) is presented.

Understanding the structure and dynamics of enzymes is important for a number of applications. Here, the authors report on the crystal structure of vanillic acid decarboxylase, and show how the dynamics of the UbiD superfamily enzymes relate to the covalent catalysis of aromatic (de)carboxylation.

PrediXcan is a widely used gene expression imputation method that links genetic variants to gene expression. Here, the authors develop EpiXcan which leverages epigenetic annotations to inform transcriptomic imputation and further use the obtained gene-trait associations for computational drug repurposing.

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.

Humans strive to design safe AI systems that align with our goals and remain under our control. However, as AI capabilities advance, we face a new challenge: the emergence of deeper, more persistent relationships between humans and AI systems. We explore how increasingly capable AI agents may generate the perception of deeper relationships with users, especially as AI becomes more personalised and agentic. This shift, from transactional interaction to ongoing sustained social engagement with AI, necessitates a new focus on socioaffective alignment—how an AI system behaves within the social and psychological ecosystem co-created with its user, where preferences and perceptions evolve through mutual influence. Addressing these dynamics involves resolving key intrapersonal dilemmas, including balancing immediate versus long-term well-being, protecting autonomy, and managing AI companionship alongside the desire to preserve human social bonds. By framing these challenges through a notion of basic psychological needs, we seek AI systems that support, rather than exploit, our fundamental nature as social and emotional beings.

Genetic variants at multiple loci of chr5p15.33 have been associated with susceptibility to numerous cancers. Here the authors show that the association of one of these loci may be explained by a variant, rs36115365, influencing telomerase reverse transcriptase (TERT) expression via ZNF148.

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.

Citizens often vote against the democracies they claim to cherish. Braley et al. find that in the United States, voters’ misperceptions about opposing partisans’ commitment to democracy may unintentionally contribute to this democratic backsliding.

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.

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

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.

Multiple myeloma, a malignancy of plasma cells, remains incurable and is poorly understood. Using next-generation sequencing of several multiple myeloma genomes reveals that this disease involves mutations of genes involved in protein translation, histone methylation and blood coagulation. The study suggests that BRAF inhibitors should be evaluated in multiple myeloma clinical trials.

Exome sequencing data from 60,706 people of diverse geographic ancestry is presented, providing insight into genetic variation across populations, and illuminating the relationship between DNA variants and human disease.

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.

Sequencing data from two large-scale studies show that most of the genetic variation influencing the risk of type 2 diabetes involves common alleles and is found in regions previously identified by genome-wide association studies, clarifying the genetic architecture of this disease.

Deep whole-genome sequencing of 300 individuals from 142 diverse populations provides insights into key population genetic parameters, shows that all modern human ancestry outside of Africa including in Australasians is consistent with descending from a single founding population, and suggests a higher rate of accumulation of mutations in non-Africans compared to Africans since divergence.

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.

ChREBP is a glucose-responsive transcription factor, which regulates glucose-mediated proliferation and cell death in pancreatic β-cells. Here the authors show that the acute feed forward induction of ChREBPβ is required for adaptive β-cell expansion, that chronic overexpression of ChREBPβ is toxic to β-cells, and offer mitigation strategies