Search

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.

Reduced glomerular filtration rate (eGFR) is a hallmark of chronic kidney disease. Here, Pattaro et al. conduct a meta-analysis to discover several new loci associated with variation in eGFR and find that genes associated with eGFR loci often encode proteins potentially related to kidney development.

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.

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 cross-ancestry meta-analysis of genome-wide association studies identifies association signals for stroke and its subtypes at 89 (61 new) independent loci, reveals putative causal genes, highlighting F11, KLKB1, PROC, GP1BA, LAMC2 and VCAM1 as potential drug targets, and provides cross-ancestry integrative risk prediction.

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.

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.

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).

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.

The International Synthetic Yeast Sc2.0 project has built Cre recombinase sites into synthetic chromosomes, enabling rapid genome evolution. Here the authors demonstrate L-SCRaMbLE, a light-controlled recombinase tool with improved control over recombination events.

By increasing NAD⁺ consumption in various organelles, mitochondria are revealed to act as buffers that help maintain subcellular NAD⁺ levels. At the same time, cells are found to be particularly sensitive to a decline in NAD⁺ levels originating from mitochondria themselves.

A study generates a clinicogenomics dataset resource, MSK-CHORD, that combines natural language processing-derived clinical annotations with patient medical data from various sources to improve models of cancer outcome.

Lean body mass is a highly heritable trait and is associated with various health conditions. Here, Kiel and colleagues perform a meta-analysis of genome-wide association studies for whole body lean body mass and find five novel genetic loci to be significantly associated.

Changes in the microenvironment of the aged lung relative to younger lung tissue can lead to the reactivation of dormant melanoma cells through a mechanism that involves a decrease in WNT5A and AXL signalling and an increase in MERTK.

The small molecule nitazoxanide (NTZ) was identified as a Wnt inhibitor by promoting protein citrullination of β-catenin through increased cytosolic calcium and PAD2 protein stabilization. β-catenin citrullination results in proteasomal degradation.

Family-based study designs have been applied to resolve confounding by population stratification, dynastic effects and assortative mating in genetic association analyses. Here, Brumpton et al. describe theory and simulations for overcoming such biases in Mendelian randomization through within-family studies.

Acral melanoma occurs on the soles of the feet, palms of the hands and in nail beds. Here, the authors reports the genomic landscape of 87 acral melanomas and find that some tumors harbor a UV signature and that the tumors are diverse at the levels of mutational signatures, structural aberrations and copy number signatures.

Integration of GWAS and single-cell transcriptomic data from the entire nervous system systematically identifies cell types underlying brain complex traits and provides insights into the etiology of Parkinson’s disease.

Primary open-angle glaucoma (POAG) is highly heritable, yet not well understood from a genetic perspective. Here, the authors perform a meta-analysis of genome-wide association studies in 34,179 POAG cases, identifying 44 previously unreported risk loci and mapping effects across multiple ethnicities.

A massive galaxy observed with the JWST indicates that the bulk of its stars formed within the first 500 million years of the Universe.

Hand grip strength as a proxy of muscular fitness is a clinical predictor of mortality and morbidity. In a large-scale GWA study, the authors find 16 robustly associated genetic loci that highlight roles in muscle fibre structure and function, neuronal maintenance and nervous system signal transduction.

Two nearby black holes are the most massive yet found, with masses—of around ten billion solar masses—considerably greater than predicted by conventional methods relating black-hole mass with the stellar velocity dispersion and bulge luminosity of the host galaxy.

A dataset of coding variation, derived from exome sequencing of nearly one million individuals from a range of ancestries, provides insight into rare variants and could accelerate the discovery of disease-associated genes and advance precision medicine efforts.

Gene regulation via genomic imprinting is found in both mammals and flowering plants, yet it remains unclear how new imprinted loci evolve. In plants, the imprinted seed development gene MEDEA has been found to have arisen by gene duplication. Its paralogue, SWINGER, has retained the ancestral function, whereas MEDEA became imprinted and acquired new function by positive Darwinian selection.

The JWST, with the aid of gravitational lensing, confirms the extreme distance of an ultra-faint galaxy at a redshift of 9.79, showing it to have a luminosity typical of the sources responsible for cosmic reionization and highly compact and complex morphology.

COVID-19 can be associated with neurological complications. Here the authors show that markers of brain injury, but not immune markers, are elevated in the blood of patients with COVID-19 both early and months after SARS-CoV-2 infection, particularly in those with brain dysfunction or neurological diagnoses.

Flexible fear-related responses may be advantageous in adolescence. Here the authors use microprisms to image prefrontal cortical spine maturation across development and report that plasticity in adolescent fear extinction responses is associated with dynamic reorganization in the amygdalahippocampal-PFC circuit.

Although termites are major human pests, they have an important role in maintaining ecosystem function and biodiversity. Here, the authors sequence the genome and transcriptomes of a dampwood termite and highlight genes that may be involved in the mechanisms underlying insect social behaviour.

Interactions of atmospheric neutrinos with quantum-gravity-induced fluctuations of the metric of spacetime would lead to decoherence. The IceCube Collaboration constrains such interactions with atmospheric neutrinos.

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