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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.

Combining 32 genome-wide association studies with high-density imputation provides a comprehensive view of the genetic contribution to type 2 diabetes in individuals of European ancestry with respect to locus discovery, causal-variant resolution, and mechanistic insight.

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.

Patricia Munroe, Christopher Newton-Cheh, Andrew Morris and colleagues perform association studies in over 340,000 individuals of European ancestry and identify 66 loci, of which 17 are novel, involved in blood pressure regulation. The risk SNPs are enriched for cis-regulatory elements, particularly in vascular endothelial cells.

Ruth Loos and colleagues report a meta-analysis of genome-wide association studies in 181,171 individuals identifying 14 new loci associated with heart rate and test these for association with cardiac conduction, rhythm disorders and cardiovascular disease. Their experimental studies in Drosophila melanogaster and zebrafish models provide support for a role for 20 candidate genes at 11 of these loci in regulation of heart rate.

The genetics and clinical consequences of resting heart rate (RHR) remain incompletely understood. Here, the authors discover new genetic variants associated with RHR and find that higher genetically predicted RHR decreases risk of atrial fibrillation and ischemic stroke.

Archaeogenetic study of ancient DNA from medieval northwestern Europeans reveals substantial increase of continental northern European ancestry in Britain, suggesting mass migration across the North Sea during the Early Middle Ages.

Abnormal blood lipid levels are important risk factors for cardiovascular and other various diseases. Here the authors conduct a large-scale multi-ethnic epigenome-wide association study combined with epigenetic (cis-QTL and eQTM) data, and identify CpG-lipid traits associations that are specific to or common across racial/ethnic groups.

Large-scale Mendelian randomization and colocalization analyses using gene expression and soluble protein data for 1,263 actionable druggable genes, which encode protein targets for approved drugs or drugs in clinical development, identify IFNAR2 and ACE2 as the most promising therapeutic targets for early management of COVID-19.

Human brain structure changes throughout the lifespan. Brouwer et al. identified genetic variants that affect rates of brain growth and atrophy. The genes are linked to early brain development and neurodegeneration and suggest involvement of metabolic processes.

The authors defined a roadmap for investigating the genetic covariance between structural or functional brain phenotypes and risk for psychiatric disorders. Their proof-of-concept study using the largest available common variant data sets for schizophrenia and volumes of several (mainly subcortical) brain structures did not find evidence of genetic overlap.

The expansion of a material in one or more directions under increasing hydrostatic pressure is a phenomenon known as negative linear compressibility. The demonstration that zinc dicyanoaurate exhibits an unusually large negative linear compressibility opens up possibilities for designing other materials with comparable properties.

Hugh Watkins, Sekar Kathiresan, Ruth McPherson, Martin Farrall and colleagues report the results of a large genome-wide association meta-analysis of coronary artery disease based on 1000 Genomes imputation. They identify ten new risk loci and show that susceptibility to this disease is largely determined by common SNPs with small effect sizes.

Samuli Ripatti and colleagues report the results of a genome-wide association study for circulating lipid levels based on 1000 Genomes Project imputation. Their results implicate several new loci, refine the association signals at many established loci and highlight the impact of low-frequency variants on lipid traits.

Borna disease virus 1 (BoDV-1) is a zoonotic pathogen endemic in bicoloured white-toothed shrews in Central Europe that can cause fatal encephalitis in humans and other mammals. Here, the authors investigate the molecular epidemiology and phylogeography of BoDV-1 using newly collected and archived samples.

Trans-ethnic analyses of exome array data identify new risk loci for type 2 diabetes. Fine-mapping analyses using genome-wide association data show that the index coding variants represent the likely causal variants at only a subset of these loci.

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.

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.

Risk for renal cell carcinoma (RCC) is higher when there are first-degree family members with the disease. Here, Scelo and colleagues perform a genome-wide association meta-analysis and new genome-wide scan to identify seven new loci with significant RCC association.

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.

Gold-standard evidence for correlates of protection is provided by analysis of a randomized phase 3 trial of Ad26.COV2.S for protection against moderate to severe-critical COVID-19 disease.

Christopher Newton-Cheh and colleagues report genome-wide association analyses for QT interval, an electrocardiographic measure reflecting myocardial repolarization, in 100,000 individuals. They identify 35 loci associated with QT interval and highlight a role for calcium regulation in myocardial repolarization.

Using data from the MONICA/KORA registry, Chen et al. show that the risk of heat-related non-fatal myocardial infarction was significantly elevated in patients receiving anti-platelet medication and beta-receptor blockers compared with non-users, and the effect of the medications was stronger in younger patients, with lower prevalence of pre-existing cardiovascular disease, compared with older patients.

Multi-ancestry genome-wide analyses identify new risk loci for age-related macular degeneration. Ancestry-specific analyses identify distinct effects at major risk loci, including smaller effect sizes for CFH risk alleles in haplotypes of African ancestry.

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.

Heart rate variability (HRV) describes the individual variation in cardiac cycle duration and is a measure of vagal control of heart rate. Here, the authors identify seventeen single-nucleotide polymorphisms associated with HRV, lending new insight into the vagal regulation of heart rhythm.

Multiancestry genome-wide association analyses identify new risk loci for stroke and stroke subtypes. Fine mapping and bioinformatics analyses of these risk loci point to mechanisms not previously implicated in stroke pathophysiology.

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.

Carotid intima-media thickness (cIMT) and plaque are associated with subclinical atherosclerosis and coronary heart disease (CHD). Here, the authors identify and prioritize genetic loci for cIMT and plaque by GWAS and colocalization approaches and further demonstrate genetic correlation with CHD and stroke.

Song et al. inferred that stridulatory wings and tibial ears co-evolved in a sexual context among crickets, katydids, and their allies, while abdominal ears evolved first in a non-sexual context in grasshoppers, and were later co-opted for courtship. They found little evidence that the evolution of these organs increased lineage diversification.

Patrick Ellinor and colleagues report meta-analyses of common and rare variant association studies for atrial fibrillation across multiple populations. They identify 12 new loci, some of which implicate genes in atrial electrical and mechanical function.

The authors transcriptionally profiled postmortem retinas from 453 age-related macular degeneration (AMD) cases and controls. Integration of AMD GWAS with eQTL analysis and TWAS identified several AMD-associated genes.

Mark Caulfield, Paul Elliott and colleagues use data from the UK Biobank to perform genome-wide association analysis for blood pressure traits. They identify and validate 107 novel loci and highlight new biological pathways for potential therapeutic intervention for hypertension.

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.

A property of oncogene-induced senescence (OIS) is the induction of a secretory phenotype, termed the senescence-associated secretome (SASP). Gil and colleagues now provide evidence that senescence can be transmitted in a paracrine manner, by showing that induction of the SASP in cells undergoing OIS by inflammasome-mediated interleukin-1 signalling can promote senescence of normal neighbouring cells.

Gil and colleagues report that mTOR affects the tumour-related effects of the senescence-associated secretory phenotype (SASP), by inhibiting the translation of the MAPKAPK2 kinase and thereby preventing the ZFP36L1-mediated SASP mRNA decay.