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Multi-ancestry genome-wide association analyses and systematic variant-to-gene mapping strategies implicate new genes and pathways influencing lung function and chronic obstructive pulmonary disease risk.

Recent results cast doubt on claims that small amounts of these drugs can benefit mental health.

One way of producing Majorana fermions for topological quantum computing is to induce superconductivity in other topological states. Here, the proximity effect does this for the quantum spin Hall effect state in a 2D material.

Free carriers and electrical polarization coexist in ferroelectric metals. Here, the authors use a capacitive method to probe the electronic compressibility of free carriers in a tunable semimetal, extract the polarized contribution, and study the carrier dependence of the ferroelectric state.

Coordination of neural activity between distant brain areas is necessary for cognition. Here, the authors report using MEG that various brain networks show dynamic phase coupling through specific frequency bands in the alpha and delta/theta range transiently during the resting state.

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

Resonances in the tunnelling spectra of a two-dimensional electron system provide strong evidence that the electrons arrange themselves into a Wigner crystal lattice with long-range ordering.

Cristen Willer and colleagues report genome-wide association analyses for blood lipid levels in 188,578 individuals. They identify 62 loci newly associated with blood lipid levels, refine the association signals at 12 loci and examine associations with cardiovascular and metabolic traits.

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.

The precise cell-type specific role of inhibitory interneurons in regulating sensory responses in the olfactory bulb is not known. Here, the authors report that removing GABAergic inhibition from one layer differentially affects response dynamics of the two main output cell types and changes odor mixture processing.

Cecilia Lindgren and colleagues report results of a large-scale genome-wide association study for waist-to-hip ratio, a measure of body fat distribution. They identify 13 new loci associated with this trait, several of which show stronger effects in women than in men.

A genome-wide association study of critically ill patients with COVID-19 identifies genetic signals that relate to important host antiviral defence mechanisms and mediators of inflammatory organ damage that may be targeted by repurposing drug treatments.

An analysis of 16 health-related quantitative traits in approximately 350,000 individuals reveals statistically significant associations between genome-wide homozygosity and four complex traits (height, lung function, cognitive ability and educational attainment); in each case increased homozygosity associates with a decreased trait value, but no evidence was seen of an influence on blood pressure, cholesterol, or ten other cardio-metabolic traits.

Activation of intracellular signaling pathways can result in MHC binding to and presentation of phosphorylated peptides. Engelhard and colleagues identify a unique phosphorylated peptide–MHC binding mode that allows solvent exposure of phosphorylated residues.

Jose Florez, Claudia Langenberg, Erik Ingelsson, Inga Prokopenko, Inês Barroso and colleagues perform large-scale association analyses using the Metabochip to gain further insights into the genetic architecture of glucose regulation. They identify 38 new loci influencing 1 or more glycemic traits and show that many of these loci also modify risk of type 2 diabetes.

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.

Sexual dimorphism in genetic vulnerability to schizophrenia, systemic lupus erythematosus and Sjögren’s syndrome is linked to differential protein abundance from alleles of complement component 4.

Any worthwhile guideline must be evidence-based, or should it? Evidence for the construction of guidelines often comes from clinical trials that are performed in the West according to the priorities and goals of that population and those of the pharmaceutical industry whose resources are relied upon to perform such trials. This Viewpoint article discusses the development of guidelines using an evidence-based approach and whether this approach is applicable worldwide.

Clinical Guidelines are primarily developed in the affluent West. This Viewpoint article discusses whether these guidelines are really useful and relevant to resource-poor, developing countries, and whether attempts to adhere to such guidelines obscure more fundamental issues such as the provision of basic health care. The authors argue that if guidelines are adapted to local resources and needs, and employ a 'cascade' approach they can work.

Evidence-based guidelines from wealthy countries define optimum goals for resource-constrained countries. This Viewpoint article discusses how health-care policy in developing countries can only be influenced through local involvement in the construction and implementation of guidelines. The authors also discuss the potential yet controversial role of the biomedical industry in facilitating the development and dissemination of global guidelines.

Monolayer transition-metal dichalcogenide (TMD) is promising to host features of topological superconductivity. Here, de la Barrera et al. study layered compounds, 2H-TaS₂ and 2H-NbSe₂, in their atomic layer limit and find a largest upper critical field for an intrinsic TMD superconductor.

Mass spectrometry analysis combined with in vitro assays reveals that SPINDLY is an O-fucosyltransferase that modifies the growth repressor DELLA and consequently enhances its activity to regulate transcription of target genes.

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.

De novo enzyme designs have generally tried to optimize multiple aspects of enzyme function simultaneously. Focusing only on positioning of active site residues to generate a nucleophilic serine as assessed by activity-based protein profiling now leads to a successful intermediate design.

The accumulation and subsequent recycling of carbonate in the crust may have helped to drive the oxygenation of the early Earth, according to an ocean and atmosphere box model incorporating the inorganic carbon cycle.

Using whole-genome data for single-nucleotide polymorphism and results from genome-wide association studies, the authors show that people’s preference for pairing with those with similar phenotypic traits has genetic causes and consequences.

Patrick Sullivan and colleagues report a multi-stage genome-wide association study for schizophrenia in a Swedish population. They identify 13 loci newly associated with schizophrenia.

In this Opinion article, Hunt and Hayden highlight that many of the models for reward-based choice are based on distinct component processes that occur in series and are functionally localized. They argue that, instead, such choice emerges from repeated computations that are undertaken in many brain areas.

The effect of sequence variants on phenotypes may depend on parental origin. Here, a method is developed that takes parental origin — the impact of which, to date, has largely been ignored — into account in genome-wide association studies. For 38,167 Icelanders genotyped, the parental origin of most alleles is determined; furthermore, a number of variants are found that show associations specific to parental origin, including three with type 2 diabetes.

Colleagues with critiques want the same thing as you: to understand the world.

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.

The sudden collapse of thawing soils in the Arctic might double the warming from greenhouse gases released from tundra, warn Merritt R. Turetsky and colleagues.

Keri Monda, Kari North, Christopher Haiman and colleagues report a meta-analysis of GWAS for body mass index that is composed of 39,144 individuals of African ancestry, followed by further genotyping in 32,268 individuals of African ancestry. The study also includes analysis of publicly available data from the GIANT consortium of ~124,000 individuals of European ancestry. The paper reports evidence for two new loci near GALNT10 and MIR148A.

Siddiqui et al. explore the role of islet-specific XBP1 expression in type 2 diabetes (T2D) and glycemic traits across diverse ancestries. XBP1 eQTL is associated with T2D, beta-cell function, HbA1c and drug response in East and South Asians in whom this variant is common and beta-cell dysfunction is a significant driver of early onset T2D.

The authors summarize the history of the ENCODE Project, the achievements of ENCODE 1 and ENCODE 2, and how the new data generated and analysed in ENCODE 3 complement the previous phases.

Owing to the growing volumes of data from high-energy physics experiments, modern deep learning methods are playing an increasingly important role in all aspects of data taking and analysis. This Review provides an overview of key developments, with a focus on the search for physics beyond the standard model.

Gonçalo Abecasis and colleagues report associations with fasting plasma glucose levels in a collection of ten genome–wide association scans from the MAGIC consortium. They find variants in the gene encoding melatonin receptor 1B that are associated with fasting glucose levels and, in a meta-analysis of 13 case-control studies, also show association with increased risk of type 2 diabetes.

A high-quality sequence assembly of the zebrafish genome reveals the largest gene set of any vertebrate and provides information on key genomic features, and comparison to the human reference genome shows that approximately 70% of human protein-coding genes have at least one clear zebrafish orthologue.