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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.

The activation and infiltration of immune cells to the vasculature is intimately linked to the immunopathology of hypertension. Here the authors implicate PI3Kγ signalling in the trafficking of CD8⁺ T cells between lymphoid and non-lymphoid organs, and the development of hypertension in a murine model.

The advantage of living in cities compared with rural areas with respect to height and BMI in children and adolescents has generally become smaller globally from 1990 to 2020, except in sub-Saharan Africa.

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.

Genome-wide association analysis in over one million individuals of European ancestry identifies 2,103 independent genetic signals (including 113 new loci) associated with blood pressure traits.

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.

Analysis of HbA1c and FPG levels across 117 population-based studies demonstrates regional variation in prevalence of previously undiagnosed screen-detected diabetes using one or both measures and suggests that use of elevated FPG alone could underestimate diabetes prevalence in low- and middle-income countries.

Inbreeding depression has been observed in many different species, but in humans a systematic analysis has been difficult so far. Here, analysing more than 1.3 million individuals, the authors show that a genomic inbreeding coefficient (FROH) is associated with disadvantageous outcomes in 32 out of 100 traits tested.

From 1980 to 2018, the levels of total and non-high-density lipoprotein cholesterol increased in low- and middle-income countries, especially in east and southeast Asia, and decreased in high-income western countries, especially those in northwestern Europe, and in central and eastern Europe.

Hundreds of genetic loci associated with age at menopause, combined with experimental evidence in mice, highlight mechanisms of reproductive ageing across the lifespan.

Trans-ancestry meta-analysis of estimated glomerular filtration rate (eGFR) from 1,046,070 individuals identifies 264 associated loci, providing a resource of molecular targets for translational research of chronic kidney disease.

Association analyses in over 1 million individuals identify 535 new loci influencing blood pressure traits. The results provide new insights into blood pressure regulation and highlight shared genetic architecture between blood pressure and lifestyle exposures.

A trans-ancestry genome-wide association study of serum urate levels identifies 183 loci influencing this trait. Enrichment analyses, fine-mapping and colocalization with gene expression in 47 tissues implicate the kidney and liver as key target organs and prioritize potential causal genes.

Chronic inflammation, marked by C-reactive protein, has been associated with changes in methylation, but the causal relationship is unclear. Here, the authors perform a Epigenome-wide association meta-analysis for C-reactive protein levels and find that these methylation changes are likely the consequence of inflammation and could contribute to disease.

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.

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.

Genome-wide analysis of self-reported dyslexia identifies 42 associated loci, including 27 not previously associated with cognitive traits. Dyslexia shows genetic correlation with ambidexterity but not neuroanatomical measures of language-related circuitry.

The mechanisms regulating the balance between proliferation and differentiation in medulloblastomas with extensive nodularity (MBEN) remain poorly understood. Here, single cell multi-omics and spatial analysis characterises the spatial tissue organisation of MBEN in the context of the developmental trajectory.

Research in 2011 regarding β-cell destruction, early immunointervention trials and development of late complications in type 1 diabetes mellitus have highlighted the heterogeneity of this disease. Patient phenotyping should be performed for the implementation of tailored therapies, especially taking into account the age at which the disease is diagnosed.

Contrary to the view that urbanization is a major driver of the global rise in obesity, the global increase in body-mass index is shown to be mostly due to increases in the body-mass indexes of rural populations.

Melinda Mills, Nicola Barban, Harold Snieder, Marcel den Hoed and colleagues perform a meta-analysis of data from over 300,000 individuals for age at first birth and number of children ever born. They identify 12 significant loci that associate with these traits, providing insights into the genetic basis of human reproductive behavior.

Variability in human longevity is genetically influenced. Using genetic data of parental lifespan, the authors identify associations at HLA-DQA/DRB1 and LPA and find that genetic variants that increase educational attainment have a positive effect on lifespan whereas increasing BMI negatively affects lifespan.

The causes of type 1 diabetes mellitus (T1DM) are unclear; however, a general consensus exists that T1DM is a T cell-mediated autoimmune disease characterized by the selective destruction of insulin-secreting β-cells. Now, two imaging mass cytometry studies of human pancreatic tissue illuminate new biology in the pathogenesis of T1DM.

Combination immunotherapies for type 1 diabetes mellitus (T1DM) that have shown promise in preclinical studies are often not effective in clinical trials, possibly because of the heterogeneity of the disease. This Review summarizes the available data about combination immunotherapies in T1DM, particularly addressing their clinical importance.

This study shows that ocular dominance plasticity (ODP) is accompanied by changes to DNA methylation at specific genes in the mouse visual cortex. The authors also show that pharmacological inhibition of the DNA methylation process can alter the functional consequence of ODP.

A large-scale GWAS provides insight on diabetes-dependent genetic effects on the glomerular filtration rate, a common metric to monitor kidney health in disease.

Delivery of siRNAs to immune cells is challenging because of these cells’ sensitivity to standard transfection reagents. This protocol describes how to synthesize an amphiphilic dendrimer and apply it to transfect siRNAs in a variety of primary immune cells.

The assignment of foods to one of four categories proposed by the Nova framework may be challenging in the absence of information on how these foods were prepared and their specific composition. A three-step iterative approach can make the categorization process more efficient and transparent, thereby increasing the accuracy of Nova estimates.