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Hrytsenko et al. analyze the role of obstructive sleep apnea (OSA) in diabetes mellitus (DM) risk using polygenic risk scores and mendelian randomization in a Hispanic and Latino community. Results reveal that OSA mediates the genetic risk for DM and there is a bidirectional causal relationship between OSA and DM.

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 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.

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.

Here the authors conduct a multi-ancestry meta-analysis of telomere length, used diverse approaches to identify genes underlying association signals, and experimentally validated POP5 and KBTBD6 as regulators of telomere length in human cells.

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.

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.

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.

Sleep duration is associated with an adverse lipid profile. Here, the authors perform genome-wide gene-by-sleep interaction analysis and find 49 previously unreported lipid loci when considering short or long total sleep time.

The Tibetan Kobresia pastures store 2.5% of the world’s soil organic carbon. Here the authors show that soil degradation and microbial shifts may irreversibly diminish the carbon sink function and accelerate nutrient losses.

Genome-wide association and fine-mapping analyses in ancestrally diverse populations implicate candidate causal genes and mechanisms underlying type 2 diabetes. Trans-ancestry genetic risk scores enhance transferability across populations.

This year marks the mid-point for the implementation of the United Nations 2030 Agenda for Sustainable Development and its 17 Sustainable Development Goals, including Sustainable Development Goal 15 ‘Life on land’. We asked a range of researchers, working across biodiversity science, conservation, policy and implementation, to reflect on priorities for action on conserving terrestrial and freshwater ecosystems over the next seven years.

Multipolar magnetic excitations are challenging to measure as most experimental probes are sensitive to dipolar processes. Here, Nag et al. show the existence of dispersing quadrupolar components to the spin excitations in an antiferromagnet, highlighting the importance of higher order magnetic excitations.

Here, the authors use passenger mutations to quantify expansion rate in ~6,000 people with mosaic chromosomal alterations in the NHLBI TOPMed cohort, finding associations between growth rate and blood counts along with germline genetic modulators of growth rate.

A meta-analysis of genome-wide association studies of type 2 diabetes (T2D) identifies more than 600 T2D-associated loci; integrating physiological trait and single-cell chromatin accessibility data at these loci sheds light on heterogeneity within the T2D phenotype.

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.

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.

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.

Polygenic risk scores have potential to predict an individual’s risk of disease based on genetic markers. Here, the authors develop a polygenic risk score for hypertension and test it in a multi-ethnic cohort, finding that the score is associated with higher likelihood of hypertension development 4-6 years later.

Here, the authors perform a rare-variant analysis of whole-genome sequence data that takes advantage of three global biobanks. They identify 29 novel rare variants associated with human height, and demonstrate an approach for identifying non-coding rare variants in regulatory regions with large effects from whole-genome sequencing data.

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.

A multi-ancestry genome-wide gene–smoking interaction study identifies 13 new loci associated with serum lipids.

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

Stephanie London, Martin Tobin and colleagues report meta-analyses of genome-wide association studies for forced vital capacity (FVC), a spirometric measure of pulmonary function that reflects lung volume. They identify six regions newly associated with FVC and demonstrate that candidate genes at these loci are expressed in lung tissue and primary lung cells.

The long-term success of area-based conservation—including both protected areas and other effective area-based conservation measures—after 2020 will depend on governments securing adequate funding and prioritizing biodiversity in land, water and sea management.

STAAR is a powerful rare variant association test that incorporates variant functional categories and complementary functional annotations using a dynamic weighting scheme based on annotation principal components. STAAR accounts for population structure and relatedness and is scalable for analyzing large whole-genome sequencing studies.

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.

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.

Sleep patterns vary and are associated with health and disease. Here Purcellet alcharacterize sleep spindle activity in 11,630 individuals and describe age-related changes, genetic influences, and possible confounding effects, serving as a resource for further understanding the physiology of sleep.

A main symptom of chronic insufficient sleep is excessive daytime sleepiness. Here, Wang et al. report 42 genome-wide significant loci for self-reported daytime sleepiness in 452,071 individuals from the UK Biobank that cluster into two biological subtypes of either sleep propensity or sleep fragmentation.

A method that allows for the detection of mosaic chromosomal alterations from blood whole-genome sequencing data highlights ancestry-specific differences in the distribution of common and rare germline susceptibility variants.

Here, the authors assess performance and limitations to polygenic risk scores in different race/ethnic groups. They find that polygenic risk score performance improves with diverse training data, and a better understanding of varying genetic backgrounds, social and environmental factors, and gene-environment interactions, is needed to enhance PRS performance for all groups.

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

GWAS have identified more than 500 genetic loci associated with blood lipid levels. Here, the authors report a genome-wide analysis of interactions between genetic markers and physical activity, and find that physical activity modifies the effects of four genetic loci on HDL or LDL cholesterol.

Sleep-disordered breathing (SDB) is a prevalent disorder linked to higher cardiovascular disease risk. Here, the authors show that summary scores reflecting SDB metabolite signatures are associated with increased risks for incident hypertension and diabetes, potentially useful in guiding risk stratification.

The team of authors led by Seon-Kyeong Jang use whole-genome sequencing data and show that rare genetic variants explain much of the ‘missing heritability’ in smoking behaviours. These results help address a long-standing mystery in behavioural genetics.

Accurate classification of genetic variants is critical for research and patient care. Here, the authors report that population-based associations between rare variants and quantitative endophenotypes for monogenic diseases can provide support for variant pathogenicity.

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.

In their analysis of two datasets, Djonlagic et al. identify 23 objective sleep metrics that predict cognitive performance and processing speed in older adults.

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.