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Analysis of the blood DNA virome in patients with COVID-19 and autoimmune disease associates endogenous HHV-6 (eHHV-6) and high anellovirus load with increased disease risk, most notably for systemic lupus erythematosus. eHHV-6 carriers show a distinct immune response.

Authors present results from a national surveillance in Japan that found MRSA strains causing bloodstream infections are predominantly from three clonal lineages. They also identified the emergence of highest 30-day-mortality MRSA clone ST764-SCCmecII and traced its evolutionary path.

The hepatitis B vaccine is recognised as the most effective approach in reducing hepatitis-B-related morbidity; vaccine-escape mutations are however capable of infecting vaccinated individuals. In this work, authors aim to establish a hepatitis B vaccine candidate, which they assess in rhesus macaques in terms of efficacy and safety.

This paper unveils the complexity of human immune cell splicing, highlighting cell-specific isoforms and establishing connections between alternative splicing and complex traits. These findings have implications for understanding diseases and the evolution of the genome.

Genome-wide analysis in 212,453 Japanese individuals identifies loci associated with 42 diseases. Comparative analysis with European populations identifies East Asian–specific associations.

Here, the authors identify six risk SNPs for systemic sclerosis by performing GWAS on Japanese patients and meta-analyzing Japanese and European GWAS datasets. Downstream analyses indicate that B cells contribute to pathogenesis.

Genome-wide analyses in BioBank Japan, UK Biobank and FinnGen identify ~5,000 new loci associated with 220 human traits. Statistical decomposition of matrices of phenome-wide summary statistics further highlights variants underpinning diseases across populations.

Characterising the clonal architecture of Adult T-cell leukemia-lymphoma (ATL) remains crucial. Here, the authors develop a capture-based sequencing panel and use deep DNA and single cell RNA sequencing and report distinct genomic and transcriptomic features associated with subclonal evolution.

This analysis of single-cell RNA sequencing data from peripheral blood mononuclear cells for 474 individuals of diverse Asian ancestries in the Asian Immune Diversity Atlas links cell-type-specific splicing variation with autoimmune and inflammatory disease risk.

Splicing QTL (sQTL), genetic variants regulating alternative splicing, can be biologically important, but complex to detect and interpret. Here, the authors identify sQTL by focusing on protein coding sequences, as an alternative to junction-based approaches.

Population-specific patterns of genomic mutations and selection of haematopoietic clones in Japanese and European participants predict the divergent rates of chronic lymphocytic leukaemia and T cell leukaemia in these populations.

Multi-ancestry genome-wide association analyses identify 124 risk loci for rheumatoid arthritis, of which 34 are novel. A polygenic risk score based on multi-ancestry data showed comparable performance between populations of European and East Asian ancestries.

EAF2 has been previously known as a transcriptional elongation factor and a proapoptotic gene lost in prostate cancer. Here the authors show that EAF2 is required for apoptosis of germinal centre B cells, and that EAF2-deficient mice develop excessive antibody responses and autoimmunity.

Histone citrullination by peptidylarginine deiminase 4 (PAD4) regulates transcription but its physiological role is unclear. Here Nakashima et al. show that PAD4 controls proliferation of multipotent haematopoietic cells by modulating c-myc expression.

PADI4 is an enzyme that converts arginine residues to citrulline. Here, Tanikawa and colleagues show that, in response to DNA damage, histone H4 and Lamin C are citrullinated in a p53 and PADI4-dependent manner andPadi4-dependent manner and Padi4 null mice are resistant to radiation-induced apoptosis in the thymus.

Genetic factors play an important part in the disease heterogeneity observed in patients with rheumatoid arthritis (RA). Genome-wide association studies (GWAS) have linked common single-nucleotide polymorphisms with the risk of developing RA, but have also highlighted the genetic heterogeneity between Asian and European patients with this disease. In this Perspectives article, the authors discuss recent advances from GWAS in Asian patients with RA, and suggest that better knowledge of the interface between genetic and environmental factors could help our understanding of the disease.

Yuta Kochi and colleagues report a meta-analysis of genome-wide association studies for rheumatoid arthritis in a Japanese population. They identify nine loci newly associated with rheumatoid arthritis in this population and consider overlap of associations with previous studies in European populations.

A genome-wide association study meta-analysis of more than 100,000 subjects of European and Asian ancestries reveals 42 new risk loci for rheumatoid arthritis, with follow-up studies identifying 98 biological candidate genes that are either already being targeted by drugs or could be in the future.

Using more than 100 independent iPSC lines derived from patients with Alzheimer’s disease, the authors discovered loci associated with the neuronal production of amyloid β and confirmed their influence using RNA interference.

This article describes the genetic heterogeneity in rheumatoid arthritis between Asian and European populations, and how these differences might underlie the pathogenesis of the disease.

Kazuhiko Yamamoto and colleagues report an association of two SNPs in CD244 with increased risk of rheumatoid arthritis. These variants promote increased expression of CD244 in luciferase reporter assays.

Swapan Nath, Sang-Cheol Bae and colleagues report the results of a large-scale association study of systemic lupus erythematosus in individuals of Asian ancestry. They identify several new susceptibility loci and find enrichment for signals near genes implicated in B cell and T cell function.

Yuta Kochi and colleagues identify a regulatory variant in CCR6 associated with susceptibility to rheumatoid arthritis. CCR6 encodes a chemokine receptor expressed on a subset of helper T cells known as Th17 cells, suggesting a possible role for CCR6 in Th17-driven autoimmunity.

Platelet activation after muscle trauma promotes extracellular trap release by macrophages and acute kidney injury.

Yuta Kochi and colleagues perform expression quantitative trait loci (eQTL) analysis on five subsets of immune cells individually sorted from blood from 105 individuals. They develop an integrated analysis pipeline of expression and epigenomic data along with gene association to identify cell-specific candidate causal genes and apply this to rheumatoid arthritis.