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Transition state theory has proven to be a powerful tool for the analysis of a number of processes, perhaps most commonly chemical reactions. Here, the authors use transition state theory to model a directly observable, micron scale process—the transport of DNA molecules in a confined environment.

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.

Clinical multi-omics data are integrated and analyzed using a generative deep-learning model.

Long colonic transit times are associated with high microbial richness and a shift towards protein catabolism, whilst short transit times are associated with a possible increase in colonic mucosa renewal.

Gluten-free diets are increasingly common in the general population. Here, the authors report the results of a randomised cross-over trial involving middle-aged, healthy Danish adults, showing evidence that a low-gluten diet leads to gut microbiome changes, possibly due to variations in dietary fibres.

A trans-ancestry meta-analysis of GWAS of glycemic traits in up to 281,416 individuals identifies 99 novel loci, of which one quarter was found due to the multi-ancestry approach, which also improves fine-mapping of credible variant sets.

Many genetic variants have been associated with human traits, but the mechanism is often unknown. Here, the authors integrate local and distal genetic associations with multi-omics datasets to provide a roadmap to understand the underlying mechanisms of GWAS variants on complex traits.

By studying individuals along a spectrum of cardiometabolic disease and adjusting for effects of lifestyle and medication, this investigation identifies alterations of the metabolome and microbiome from dysmetabolic conditions, such as obesity and type 2 diabetes, to ischemic heart disease.

An analysis of 2,173 individuals from the MetaCardis cohort quantifies the individual and combinatorial effects of a range of drugs on host health, metabolome and gut microbiome in cardiometabolic disease.

TMAO is known to be atherothrombotic. Here the authors show that i) kidney function is the main determinant of serum TMAO, ii) TMAO increases kidney scarring with TGF-β1 signalling and iii) anti-diabetic drugs with reno-protective properties such as GLP1R agonists reduce plasma TMAO.

Spinal CPGs transmit movement commands through rhythmic synaptic drive onto the spinal premotor network. Here, the authors use paired recordings to demonstrate that spinal neurons have decorrelated synaptic activity suggesting a CPG network with sparse convergent connectivity.

A cross-sectional analysis of participants in the MetaCardis Body Mass Index Spectrum cohort finds that the higher prevalence of gut microbiota dysbiosis in individuals with obesity is not observed in those who take statin drugs.

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.

Gut microbial metabolism of nutrients contributes to metabolic diseases, and the histidine metabolite imidazole propionate (ImP) is produced by type 2 diabetes (T2D) associated microbiome. Here the authors report that circulating ImP levels are increased in subjects with prediabetes or T2D in three European populations, and this increase associates with altered gut microbiota rather than dietary histidine.

Data from over 700,000 individuals reveal the identity of 83 sequence variants that affect human height, implicating new candidate genes and pathways as being involved in growth.

Genome-wide association studies (GWAS) have become a key tool to discover genetic markers for complex traits; however, environmental factors that interact with genes are rarely considered. Here, the authors conduct a GWAS of obesity traits, and find that smoking may alter genetic susceptibilities.

This meta-analysis of genome-wide association studies identifies four genetic loci associated with circulating leptin levels independent of adiposity. Examination in mouse adipose tissue explants provides functional support for the leptin-associated loci.

A study presents ensemble recordings of neurons in the lumbar spinal cord indicating that activity in spinal cord circuits for movement follows low-dimensional rotational dynamics, and proposes a theory of neural generation of movements.

The levels of 1,251 metabolites are measured in 475 phenotyped individuals, and machine-learning algorithms reveal that diet and the microbiome are the determinants with the strongest predictive power for the levels of these metabolites.

Exome-wide analysis identifies rare and low-frequency coding variants associated with body mass index. Gene-based meta-analysis and functional studies implicate 13 genes, eight of which are novel, and neuronal pathways as factors in human obesity.

Single molecule methods for measuring load dependence are fundamental for molecular motor research. Here, Sung et al. introduce harmonic force spectroscopy, a method that randomly applies varying loads at high frequency, allowing the determination of load dependent parameters of human β-cardiac myosin at physiological ATP concentration.

Bjarke Feenstra and colleagues identify common variants at six loci associated with general or MMR vaccine–related febrile seizures. The two loci specifically associated with MMR-related febrile seizures harbor the interferon-stimulated gene IFI44L and the measles virus receptor gene CD46.

Growing evidence from metagenome-wide association studies link multiple common disorders to microbial dysbiosis but effects of drug treatment are often not accounted for; here, the authors re-analyse two previous metagenomic studies of type 2 diabetes mellitus patients together with a novel cohort to determine the effects of the widely prescribed antidiabetic drug metformin and highlight the need to distinguish the effects of a disease from the effects of treatment on the gut microbiota.

Unnur Thorsteinsdottir, Kari Stefansson and colleagues identify low-frequency and rare sequence variants associated with elevated or reduced risk of type 2 diabetes. The newly discovered variants include an intronic variant associated with altered expression of CCND2, two independent missense variants in PAM and a rare frameshift variant in PDX1.