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This meta-analysis of 42 studies finds that learning progress has slowed during the coronavirus disease 2019 pandemic, particularly among children from low socio-economic backgrounds and in poorer countries. Reported learning deficits were larger in maths than in reading.

Limited diagnostic capacity for asymptomatic individuals hinders malaria elimination efforts in Africa. Here, the authors present a near point-of-care method based on colorimetric LAMP detection that outperforms expert microscopy and commercial rapid diagnostic tests for Plasmodium detection in asymptomatic and submicroscopic individuals.

Predicting cancer risk requires large datasets and sophisticated models. Here the authors integrate polygenic risk scores and modifiable risk factors for multiple cancers in the UK Biobank, improving general risk prediction and distinguishing cases where genetic or lifestyle factors have stronger associations.

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.

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.

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.

A multi-omics approach reveals host–microbiome interactions in aging in mice.

The role of impaired lung function in lung cancer etiology is complex due to the relation of cigarette smoking to both conditions. Here, supported by Mendelian randomization analysis the authors find a link between pulmonary function impairment and lung cancer risk beyond smoking, implicating immune-related pathways

MRI data from more than 100 studies have been aggregated to yield new insights about brain development and ageing, and create an interactive open resource for comparison of brain structures throughout the human lifespan, including those associated with neurological and psychiatric disorders.

Genome-wide association analyses of intracranial and nine subcortical brain volumes in 74,898 participants of European ancestry identify 254 independent loci and yield polygenic scores accounting for brain variation across ancestries.

Georgakopoulos-Soares, Yizhar-Barnea, Mouratidis et al. identify neomers, short (16 base pair) DNA sequences that are absent in the genomes of healthy individuals but appear in tumors due to mutations. They show that neomers can accurately detect cancer from cell-free DNA and that neomers found in gene regulatory elements can alter regulatory activity.

Meta-analysis of genome-wide association studies on Alzheimer’s disease and related dementias identifies new loci and enables generation of a new genetic risk score associated with the risk of future Alzheimer’s disease and dementia.

Cortex morphology varies with age, cognitive function, and in neurological and psychiatric diseases. Here the authors report 160 genome-wide significant associations with thickness, surface area and volume of the total cortex and 34 cortical regions from a GWAS meta-analysis in 22,824 adults.

Ruth Loos and colleagues report results of a large genome-wide association study for body mass index. They identify 18 new loci associated with this trait, some of which map near key hypothalamic regulators of energy balance.

A cross-ancestry genome-wide association meta-analysis of lung cancer including 61,047 cases and 947,237 controls identifies five new cross-ancestry susceptibility loci and highlights ancestry-specific effects of common and rare variants on lung cancer risk.

DNA methylation is an age biomarker, but nonlinear aspects of its age-related dynamics are not well characterized. Here, the authors identify loci that undergo sudden methylation changes at specific life stages in the aging colon of male mice.

A cross-ancestry genome-wide association meta-analysis of amyotrophic lateral sclerosis (ALS) including 29,612 patients with ALS and 122,656 controls identifies 15 risk loci with distinct genetic architectures and neuron-specific biology.

Castells-Nobau et al. provide insight into how bacteriophages in the gut microbiome contribute to regulating food addiction by modulating tryptophan and tyrosine metabolism in the host.

Chini et al. demonstrate that CD38⁺ expression in immune cells increases during aging, owing to the senescence-associated secretory phenotype of senescent cells, and the ecto-enzymatic activity of CD38⁺ affects intracellular NAD⁺ levels in vivo by hydrolyzing the NAD⁺ intermediate nicotinamide mononucleotide extracellularly.

Genome-wide analysis identifies variants associated with the volume of seven different subcortical brain regions defined by magnetic resonance imaging. Implicated genes are involved in neurodevelopmental and synaptic signaling pathways.

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.

An increase in the volume of the brain lateral ventricles is a sign of normal aging, but can also be associated with neurological and psychiatric disorders. Here, Vojinovic et al. identify seven genetic loci in a GWA study for ventricular volume in 23,500 individuals and find correlation with thalamus volume.

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.

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.

Organismal ageing is driven by conserved biological processes. Here the authors build on a comparative RNA-seq analysis in three model organisms to demonstrate that the gene, bcat-1, which catalyses the degradation of branched-chain amino acids, regulates lifespan in worms.

Over one hundred loci have been identified to be associated with the familial risk of prostate cancer but the functional effects are poorly understood. Here the authors use single-nucleotide variant and epigentic data to show an underlying genetic architecture marked by histone modification.

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.

Better analytical methods are needed to extract biological meaning from genome-wide association studies (GWAS) of psychiatric disorders. Here the authors take GWAS data from over 60,000 subjects, including patients with schizophrenia, bipolar disorder and major depression, and identify common etiological pathways shared amongst them.

The goal of the 1000 Genomes Project is to provide in-depth information on variation in human genome sequences. In the pilot phase reported here, different strategies for genome-wide sequencing, using high-throughput sequencing platforms, were developed and compared. The resulting data set includes more than 95% of the currently accessible variants found in any individual, and can be used to inform association and functional studies.

Ageing is associated with a pronounced shift in mortality from cancer to degenerative diseases. Here, the authors show that in concordance with this shift, conserved transcriptional alterations during ageing across four vertebrates align with degenerative diseases but are opposite to those in cancer.

Cardiac rehabilitation, in most developed countries, is a proven means of reducing mortality but it is grossly underutilized owing to factors involving both the health system and patients. These issues have not been investigated concurrently. In this paper the authors describe a prospective study with a multilevel design to show that the most relevant physician perceptions of such programs are program quality and perceived benefit. For patients, they are barriers to cardiac rehabilitation, which might be conveyed during pre-referral discussions. Work to improve physicians' perceptions and patients' understanding of rehabilitation services might improve use.

There are various measures to quantify the contribution of genetic variants to disease risk, but differing terminology and assumptions obfuscate their use and interpretation. In this Analysis, the authors consider and contrast six commonly used measures that assess disease risk of individual variants, and provide numerical examples in breast cancer, Crohn's disease, rheumatoid arthritis and schizophrenia.

Systemic sclerosis (SSc) is a heterogeneous chronic autoimmune disease that affects the connective tissue. Here, López-Isac et al. identify 13 new risk loci for SSc as well as loci specific for limited cutaneous and diffuse SSc and, defining credible sets and performing functional annotation, highlight key pathways and cell types for SSc.

Recent genome-wide association and expression array studies have provided new insights into prostate cancer genetics. The germline and somatic variants identified in these studies have been proposed to predict prostate cancer risk and aggressiveness. These results are discussed in the context of their implications for the screening and treatment of prostate cancer.

Renal manifestations in Crohn's disease—a chronic relapsing inflammatory disease characterized by mucosal ulcerations of the digestive tract—are rare. Tubulointerstitial nephritis has been reported in Crohn's disease, but most cases have occurred in patients treated with 5-aminosalicylic acid derivatives, which are known to be nephrotoxic. In this Case Study, Waters et al. present two cases of tubulointerstitial nephritis occurring in patients with Crohn's disease, and emphasize that physicians should be aware of this serious and under-recognized complication.

Several new recommendations for the vaccination of adults with autoimmune inflammatory diseases could represent an important step forward in the prevention of infections in these high-risk patients.

The ability to provide information about variants in genes is crucial to genome-wide association studies. This article argues that the currently available marker sets are unlikely to provide adequate coverage of genic variants, and suggests how this problem could be overcome.

Cardiac rehabilitation can reduce cardiovascular risk factors and prevent cardiac morbidity and mortality as part of a comprehensive secondary-prevention strategy. However, evidence indicates that cardiac rehabilitation programs are currently underutilized, primarily because many patients are not referred to these programs by their health-care providers. The authors of this Review examine how novel referral strategies can help to improve cardiac rehabilitation referral and enrollment rates.

Using the lifespan brain chart and two large-scale cross-cultural consortia (ABIDE and CABIC), we disentangle the heterogeneity of brain morphology in ASD into two structural impairment pathways that could disrupt sensory to association functions.

Psychological stress is thought to contribute to the cardiovascular disease process at several stages, including the long-term development of coronary heart disease and acute triggering of cardiac events. In this Review, Steptoe and Kivimäki summarize the evidence for the association between stress and cardiovascular disease, with a focus on external work-related and social stressors. They also discuss the effects of stress-management strategies on cardiovascular health.

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.