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In this Stage 2 Registered Report, Buchanan et al. show evidence confirming the phenomenon of semantic priming across speakers of 19 diverse languages.

In summer 2022 an enormous fish kill was observed in the Oder River as a consequence of prymnesins produced by an algal bloom. An investigation of the exposure of aquatic life and human cells to the contaminated Oder water revealed the presence of neurotoxicants, which are attributed to B-type prymnesins, with minor contributions by organic micropollutants.

The climate action simulation exercise increased participants’ knowledge about high-impact climate actions and policies, and those gains persisted for at least 6 months, according to survey data and statistical analysis.

Meta-analyses in up to 1.3 million individuals identify 87 rare-variant associations with blood pressure traits. On average, rare variants exhibit effects ~8 times larger than the mean effects of common variants and implicate candidate causal genes at associated regions.

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

Infectious and chronic diseases display seasonal patterns, yet seasonal changes in physiology are rarely thought to affect human health. Here the authors show seasonal variation in all major blood cells and in gene and protein expression in diverse tissues, suggesting a mechanism for seasonal disease proneness and physiology.

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.

John Harty and colleagues report that, in mouse models of malaria, regulatory T cells expand, as in humans, and inhibit conventional T cells and germinal center B cells, thereby impairing protective responses against blood-stage disease. Timed blockade of the inhibitory receptor CTLA-4 cured infection in mice and promoted cross-protective blood-stage immunity against a different Plasmodium species.

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.

Patricia Munroe, Joanna Howson and colleagues genotype ∼350,000 individuals and identify 30 new blood pressure– or hypertension-associated risk loci. Their analyses provide insights into the pathophysiology of hypertension and highlight new potential targets for clinical intervention.

Systemic sclerosis (SSc) is a fibrotic disease affecting multiple organs. Here the authors use patient samples plus mouse studies to show a central role for tenascin C as a TLR4 activator responsible for persistence of fibrosis in the context of SSc and SSc-like disease.

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.

A dataset of coding variation, derived from exome sequencing of nearly one million individuals from a range of ancestries, provides insight into rare variants and could accelerate the discovery of disease-associated genes and advance precision medicine efforts.

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.

Sequencing data from two large-scale studies show that most of the genetic variation influencing the risk of type 2 diabetes involves common alleles and is found in regions previously identified by genome-wide association studies, clarifying the genetic architecture of this disease.

The mechanisms that drive the diverse disease manifestations and increased cancer risk associated with systemic sclerosis are unclear. Investigating the genomic alterations observed in patients with systemic sclerosis could contribute towards untangling this complex disease.

Systemic sclerosis (SSc) is an autoimmune disease causing skin fibrosis and organ inflammation. Here the authors generate and analyze SSc skin single cell RNA sequencing data to propose contributions from both myofibroblasts and endothelial-to-mesenchymal -transitioning cells (EndoMT) to skin fibrosis, and to implicate the involvement of Hippo signaling pathways.

Fibrosis of the skin and other organs is a key feature of systemic sclerosis (SSc). Studies performed during the past decade have provided a more detailed insight to the cellular and immune mechanisms underlying the fibrotic process in SSc. In this Review, the authors describe these important recent findings, and how our improved understanding of SSc fibrosis has facilitated the development of potential targeted therapies.

Jose Florez, Claudia Langenberg, Erik Ingelsson, Inga Prokopenko, Inês Barroso and colleagues perform large-scale association analyses using the Metabochip to gain further insights into the genetic architecture of glucose regulation. They identify 38 new loci influencing 1 or more glycemic traits and show that many of these loci also modify risk of type 2 diabetes.

A20 gene variants are linked with systemic sclerosis (SS), but the mechanisms are unclear. Here, the authors show that A20 expression is reduced in SS skin and lungs, that its ablation in mice induces SS, and that show that fibrosis can be ameliorated by induction of A20.

Patients with systemic sclerosis present with varying clinical features, have different responses to therapy, and end up with different outcomes. Categorizing patients improves disease management. A new study now proposes that patients with systemic sclerosis and overlapping features of another connective tissue disease might form a distinct disease subset.

Several strands of new research indicate that skin-specific adipocyte progenitor cells regulate myofibroblasts and skin fibrosis in scleroderma.

Exome-wide genetic analysis on >300,000 individuals identifies associations with plasma lipid traits. Loci significantly associated with cholesterol and triglycerides are examined together to determine the effects of alleles on type 2 diabetes and coronary artery disease risk.

The adipokine endotrophin promotes tumour inflammation and angiogenesis, but its effects on adipose tissue are unclear. Here, Sun et al.show that endotrophin promotes adipose tissue inflammation and fibrosis, and that injections of an anti-endotrophin antibody improve metabolic parameters of mice on a high-fat diet.

Xue and colleagues show that Runx3^−/− CD8⁺ T effector cells aberrantly upregulate genes characteristic of T_FH cell lineage and exhibit impaired induction of cytotoxic molecules.

In patients with systemic sclerosis, impaired activity of transforming growth factor β (TGF-β) has a central role in the pathogenesis of fibrosis, which leads to the progression of the disease and severe organ damage. In this context, the authors discuss the mechanisms of aberrant TGF-β signaling and highlight the potential of TGF-β as a therapeutic target in systemic sclerosis.

Adenomyoepithelioma is a rare tumor of the breast with an unknown genetic basis. Here the authors perform a genomic analysis of adenomyoepitheliomas revealing that their repertoire of somatic mutations vary according to the estrogen receptor (ER) status, and that ER-negative tumors harbor recurrent mutations in HRAS and PI3K pathway genes.

The diagnosis, treatment and management of systemic sclerosis (SSc) remains challenging, owing to the complexity of this disease. In this Perspective, an international group of experts discuss the future of SSc research and how the advent of innovative technologies will advance research into and understanding of SSc.