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Genome-wide analyses identify 30 independent loci associated with obsessive–compulsive disorder, highlighting genetic overlap with other psychiatric disorders and implicating putative effector genes and cell types contributing to its etiology.

Genomic analyses applied to 14 childhood- and adult-onset psychiatric disorders identifies five underlying genomic factors that explain the majority of the genetic variance of the individual disorders.

Here the authors combine a deep generative model with structure-based drug design and prospectively validate functionally active, nanomolar, A_2A adenosine receptor ligands and solve their crystal structures to close the Artificial Intelligence Structure-Based Drug Design loop.

Polygenic scores for body mass index and obesity constructed using data from 5 million people with different ancestries were associated with distinct weight gain trajectories from early childhood to adulthood.

A generative artificial intelligence-powered method enables de novo design of highly active enzymes based on information about the geometry of residues in the active site, without requiring protein backbone or sequence information.

A global network of researchers was formed to investigate the role of human genetics in SARS-CoV-2 infection and COVID-19 severity; this paper reports 13 genome-wide significant loci and potentially actionable mechanisms in response to infection.

Mass-wasting deposits that accumulated against mid-ocean ridge faults have high porosity in which calcium carbonate precipitated, storing seawater carbon dioxide, as revealed by cores of a 61-million-year-old seafloor talus deposit.

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.

Samples returned from asteroid Bennu contain bio-essential sugars such as ribose and glucose that may have formed in the parent asteroid from brines containing formaldehyde, according to a geochemical study.

The hippocampus in mammalian brain varies in size across individuals. Here, Hibar and colleagues perform a genome-wide association meta-analysis to find six genetic loci with significant association to hippocampus volume.

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.

A genome-wide association meta-analysis study of blood lipid levels in roughly 1.6 million individuals demonstrates the gain of power attained when diverse ancestries are included to improve fine-mapping and polygenic score generation, with gains in locus discovery related to sample size.

A large genome-wide association study of more than 5 million individuals reveals that 12,111 single-nucleotide polymorphisms account for nearly all the heritability of height attributable to common genetic variants.

The protein p53 responds to DNA damage and intracellular infection by activating pathways that arrest the cell cycle, repair DNA, and elicit apoptosis. Here, Allen et al. show that the obligate intracellular bacterium Orientia tsutsugamushi inhibits p53 expression and protects host cells from DNA damage, thus delaying apoptosis and favouring bacterial replication.

A study that tracked mammal populations before, during and after a severe storm in Mozambique’s Gorongosa National Park finds that behavioural responses and survival are linked to body size, with increased mortality of small species owing to limited mobility and changes in food availability.

An analysis of 24,202 critical cases of COVID-19 identifies potentially druggable targets in inflammatory signalling (JAK1), monocyte–macrophage activation and endothelial permeability (PDE4A), immunometabolism (SLC2A5 and AK5), and host factors required for viral entry and replication (TMPRSS2 and RAB2A).

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.

Whole-genome sequencing, transcriptome-wide association and fine-mapping analyses in over 7,000 individuals with critical COVID-19 are used to identify 16 independent variants that are associated with severe illness in COVID-19.

Viruses and bacteria are known to subvert the immune system using mimic or inhibitory proteins. Here the authors show that the protein Ank5 from the bacterium Orientia tsutsugamushi inhibits nuclear translocation and promotes proteasomal degradation of the MHC class I gene transactivator NLRC5.

Parity induces an accumulation of CD8⁺ T cells, including cells with a tissue-resident-memory-like phenotype within human normal breast tissue, offering long-term protection against triple-negative breast cancer.

Agriculture sustains a large and growing human population, but generates widespread impacts. This study assesses the health effects of air pollution caused by maize production. Reduced air quality leads to 4,300 premature deaths annually in the United States, akin to US$39 billion in damages, and climate change damages of US$4.9 billion.

Common genetic variants associated with plasma lipids have been extensively studied for a better understanding of common diseases. Here, the authors use whole-genome sequencing of 16,324 individuals to analyze rare variant associations and to determine their monogenic and polygenic contribution to lipid traits.

Genome-wide association analyses, functionally informed fine-mapping and complementary gene prioritization approaches identify new risk loci and candidate effector genes for CAD.

The most common protein modification in eukaryotes is N-terminal acetylation, but its functional impact has remained enigmatic. Here, the authors find that a key role for N-terminal acetylation is shielding proteins from ubiquitin ligase-mediated degradation, mediating motility and longevity.

This overview of the ENCODE project outlines the data accumulated so far, revealing that 80% of the human genome now has at least one biochemical function assigned to it; the newly identified functional elements should aid the interpretation of results of genome-wide association studies, as many correspond to sites of association with human disease.

Mark McCarthy, Michael Boehnke, Andrew Morris and colleagues perform large-scale association analyses using the Metabochip to gain insights into the genetic architecture of type 2 diabetes. They report several new susceptibility loci, including two that show sex-differentiated effects on disease risk.

Elucidation of the mechanism by which zeta inhibitory peptide erases memories, involving endocytosis of AMPA receptors on potentiated synapses, provides insight into more general mechanisms of memory maintenance and response to traumatic brain injury.

Openshaw and colleagues find myeloid inflammation and complement activation signatures in patients with long COVID who were previously hospitalized.

Rare variant association data from human genetics combined with in vitro and in vivo functional validation highlight ANGPTL7 as a promising therapeutic target for intraocular pressure reduction, and protection from glaucoma.

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.

Kyle Gaulton, Mark McCarthy, Andrew Morris and colleagues report fine mapping and genomic annotation of 39 established type 2 diabetes susceptibility loci. They find that the set of potential causal variants is enriched for overlap with FOXA2 binding sites in human islet and liver cells, and they show that a likely causal variant near MTNR1B increases FOXA2-bound enhancer activity, providing a molecular mechanism to explain the effect of this locus on disease risk.

The raptorial appendages of stomatopods are known to inflict large impact forces at high speeds, while exhibiting large damage tolerance. Here, the authors study the structure, distribution and nanomechanical properties of mineral phases in stomatopod's clubs, finding that calcium sulphate is co-localized with crystalline fluorapatite.

Bosonic qubits can be engineered to feature intrinsic protection against certain kinds of errors, which makes quantum error correction across many bosonic qubits possible with less overhead.

Applying magnetic and electric fields to twisted bilayer graphene creates an electron–hole bilayer that features helical 1D edge modes and fractional quantum Hall states.

Flash droughts can have devastating impacts but are notoriously difficult to predict. This study identifies global hotspots of flash drought, driven by evaporative demand and precipitation deficits across varying geographic regions and crop-type, providing a framework for flash drought prediction.

A multi-ancestry meta-regression study analyses diverse genome-wide association studies and genome loci associated with tobacco and alcohol use.

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 genome-wide association meta-analysis, it is often difficult to find an independent dataset of sufficient size to replicate associations. Here, the authors have developed MAMBA to calculate the probability of replicability based on consistency between datasets within the meta-analysis.

Alzheimer’s disease has been associated with increased structural brain aging. Here the authors describe a model that predicts brain aging from resting state functional connectivity data, and demonstrate this is accelerated in individuals with pre-clinical familial Alzheimer’s disease.

Species sharing a common enemy such as a parasitoid or predator can indirectly affect one another. Here, Frost et al. use quantitative food-web data from communities of caterpillar hosts to show experimentally that apparent competition is important in predicting food-web structure across habitats.

It is unclear whether plant-herbivore interactions systematically favour exotic plant species. Here the authors investigate plant-herbivore and plant-soil biota interactions in experimental mesocosm communities, finding that exotic plants dominate community biomass despite accumulating more invertebrate herbivores.

It is important to understand the mechanisms of thermally induced battery degradation and any safety hazards. Here, the authors use high-speed synchrotron radiation X-ray computed tomography to shed light on the structural and thermal dynamics associated with thermal runaway and failure of commercial Li-ion batteries.

In this study, Aggarwal and colleagues perform prospective sequencing of SARS-CoV-2 isolates derived from asymptomatic student screening and symptomatic testing of students and staff at the University of Cambridge. They identify important factors that contributed to within university transmission and onward spread into the wider community.