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Our understanding of the functional link between differential DNA methylation and type 2 diabetes and obesity remains limited. Here the authors present a blood-based EWAS of fasting glucose and insulin among 4808 non-diabetic Europeans and identify nine CpGs not previously implicated in glucose, insulin homeostasis and diabetes.

A study of genetic associations identifies 46 new loci associated with alcohol consumption. By assessing their function and potential pleiotropy, the authors suggest genetic mechanisms that are shared with neuropsychiatric disorders, including schizophrenia.

Exploring the clonal expansion of somatically mutated hematopoietic stem cells with aging, Mack, Raddatz et al. quantify rates of clonal expansion in 4,370 individuals in the Trans-Omics for Precision Medicine cohort, observing epigenetic and proteomic patterns associated with clonal hematopoiesis of indeterminate potential.

The same type of polymer network deforms cell membranes inward, to absorb external material, and outward, to facilitate signal transmission. Experiments and theory show that these deformations are regulated by membrane tension and network mesh size.

Mutations in the gene HADHA result in mitochondrial tri-functional protein (MTP) deficiency and can result in sudden infant death syndrome for which there is no treatment. Here the authors show that the MTP deficient pathology in human cardiomyocytes leads to an abnormal cardiolipin pattern and suggests that cardiolipin affecting compounds may serve as a potential therapy.

Using data from a large US population survey, Choi et al. investigated the nuanced associations between perceived social support and the risk for depression during the COVID-19 pandemic.

High-resolution subnational mapping of child growth failure indicators for 105 low- and middle-income countries between 2000 and 2017 shows that, despite considerable progress, substantial geographical inequalities still exist in some countries.

Cancer cells possess unique molecular features that can confer an increased dependence on specific genes. Here, the authors use CRISPR-Cas9 screens to identify selectively essential genes and therapeutic targets in chordoma.

Common genetic variants associated with plasma lipids have been extensively studied for a better understanding of common diseases. Here, the authors use whole-genome sequencing of 16,324 individuals to analyze rare variant associations and to determine their monogenic and polygenic contribution to lipid traits.

Circulating lipoprotein(a) is an important risk factor for cardiovascular disease and shows variability between different ethnic groups. Here, Zekavat et al. perform whole-genome sequencing in individuals of European and African ancestries and find ancestry-specific genetic determinants for lipoprotein(a) levels.

Genetic variants at multiple loci of chr5p15.33 have been associated with susceptibility to numerous cancers. Here the authors show that the association of one of these loci may be explained by a variant, rs36115365, influencing telomerase reverse transcriptase (TERT) expression via ZNF148.

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.

Several GWAS have identified many common variants associated with blood metabolites. Here, the authors use an exome array to identify low frequency, potentially functional variants that impact human metabolism.

The non-processive motor protein myosin 1b is required for Golgi membrane tubulation. Using a minimal reconstituted system and theoretical analysis, Yamada et al.demonstrate that the mechanism of tubule extraction depends on the catch bond properties of myosin 1b.

An atlas of the substrate specificities for the human tyrosine kinome reveals diversity of motif specificities and enables identification of kinase–substrate relationships and kinase regulation in phosphoproteomics experiments.

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.

Ant pupae secrete a fluid, derived from the moulting fluid, that elicits parental care behaviour, provides nutrients for larvae and must be removed for pupal survival.

Many aging-related phenotypes share a common genetic component, but to disentangle disease-specific variants from aging-specific ones has been challenging. Here Timmers et al. combined several genetics studies of aging-related traits to identify common underlying genetic factors that contribute to aging.

Incorporating gold nanowires into scaffolds used to create heart patches can improve electrical communication between cells and enhance the growth of tissues.

CD32a expression is induced on the surface of HIV-1-infected quiescent CD4 T cells, and could thus be used as a biomarker to facilitate future study of how the virus persists in cellular reservoirs in infected hosts.

Emelia Benjamin and colleagues report a meta-analysis of genome-wide association study data for atrial fibrillation, a condition associated with stroke and heart failure, in five European community-based cohorts of the CHARGE consortium. They report an association in ZFHX3 to atrial fibrillation, with replication in an independent cohort from the German AF Network.

Proteome analysis of The Cancer Genome Atlas (TCGA) colorectal cancer specimens reveals that DNA- or RNA-level measurements cannot reliably predict protein abundance, colorectal tumours can be separated into distinct proteotypes, and that copy number alterations drive mRNA abundance changes but few extend to protein-level changes.

MetaSTAAR enables functionally informed rare variant association analysis in biobank-scale cohorts using an efficient, sparse matrix approach for summary statistic storage.

Prior exposure to infectious agents can impact the vaccination induced immune response. Here the authors show prior SARS-CoV-2 infection results in more efficient induction of mucosal SARS-CoV-2 secretory IgA antibody following mRNA vaccination.

Roger Milne and colleagues conduct a genome-wide association study for estrogen receptor (ER)-negative breast cancer combined with BRCA1 mutation carriers in a large cohort. They identify ten new risk variants and find high genetic correlation between breast cancer risk for BRCA1 mutation carriers and risk of ER-negative breast cancer in the general population.

Here, Rathnasinghe et al. characterize the pathogenesis of a mouse-adapted SARS-CoV-2 in infected obese and aged mice, and identify mutations that are present in SARS-CoV-2 variants of concern, associated with higher transmissibility.

The genetic factors involved in disease progression and drug resistance in multiple myeloma (MM) are varied and complex. Here, genomic and transcriptomic profiling of 511 relapsed and refractory MM patients reveals genetic alterations in several oncogenic pathways contributing to progression and resistance to MM therapies.

Here, the authors present results of the ZiBRA-2 project (https://www.zibra2project.org) which is an arbovirus surveillance project, across the Midwest of Brazil using a mobile genomics laboratory, combined with a genomic surveillance training program that targeted post-graduate students, laboratory technicians, and health practitioners in universities and laboratories.

CRISPR-mediated gene knockout and activation are used to identify molecules in cancer cells and macrophages that regulate antibody-dependent cancer cell phagocytosis.

Resources reporting RNA editing sites from brain tissue have been published. Here, the authors provide an atlas of RNA editing events found in the aged and Alzheimer’s disease human brain tissue resulting in changes at protein level.

Tryptophan depletion in melanoma cells after prolonged treatment with interferon-γ (IFNγ) results in ribosomal frameshifting and the production of aberrant peptides that can be presented to T cells and induce an immune response.

An artificial intelligence system that can engage in a competitive debate with humans is presented.

This Registered Report presents evidence from 87 countries and regions showing that brief emotion-regulation interventions consistently reduced negative emotions and increased positive emotions during the COVID-19 pandemic.

Enhancer variants associated with red blood cell traits alter signaling transcription factor motifs, leading to changes in expression of genes that are upregulated during erythroid differentiation.

The outlet glaciers that comprise the Northeast Greenland Ice Stream (NEGIS) have experienced accelerated retreat in recent years, yet their longterm stability remains unclear. Here, via cosmogenic surface exposure and radiocarbon ages, the authors investigate the stability of the NEGIS for the past 45 kyr.

Differentially methylated CpGs can inform on disease mechanisms and be useful as biomarkers. Here, the authors perform GWAS for DNA methylation in whole blood, cis- and trans-meQTL mapping, followed by Mendelian randomization analysis that links meQTLs with cardiovascular diseases.

Epigenetic clocks based on DNA methylation levels are estimators of chronological age. Here, the authors perform a GWAS of epigenetic aging rates in blood and find SNP variants in the TERT locus associated with increased intrinsic epigenetic age are also associated with longer telomeres.

Existing plant pan-genomic studies usually report considerable intraspecific whole gene presence-absence variation. Here, the authors use pan-genomic approach to reveal gradual polyploid genome evolution by analyzing of Brachypodium hybridum and its diploid progenitors.

Influenza viremia is rare in human blood and not well studied. Here, the authors show that influenza can be found in human platelets and that platelet engulfment of influenza A results in TLR7-dependent C3 release, which in turn promotes neutrophil-DNA release and formation of platelet-DNA aggregates.

Oxidized host-derived phospholipids such as oxPAPC can play important roles in atherosclerosis. Zanoni and colleagues demonstrate that oxPAPC generates a distinctive metabolic and hyperinflammatory profile in macrophages that can drive atherosclerosis in mice.

Septins are cytoskeletal filaments that localize at constriction sites and impact membrane remodeling. Here authors examine the curvature sensitivity of septins using bilayers on wavy patterns and derive a theoretical model that quantitatively describe the results.

A system employing liquid-handling robotics and an integrated mobile microscope enables the automated culture, sample collection and in situ microscopy imaging of up to ten fluidically coupled organ chips within a standard tissue-culture incubator.

Memory lapses can occur due to ineffective encoding, but it is unclear if targeted brain stimulation can improve memory performance. Here, authors use a closed-loop system to decode and stimulate periods of ineffective encoding, showing that stimulation of lateral temporal cortex can enhance memory.