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Analyses in BioBank Japan, UK Biobank and Tohoku Medical Megabank show that polygenic scores constructed from subgroups stratified by body mass index (BMI) can optimize type 2 diabetes risk prediction, particularly among individuals with low BMI.

Intracranial germ cell tumors (IGCTs) are rare brain tumors mainly diagnosed in children and young adults. Here, the authors conduct a genome-wide association study for IGCTs, identify a risk locus at BAK1, and characterize its functional consequences.

Here, the authors perform a genome-wide association study for recurrent pregnancy loss without apparent clinical causes and identify a protective HLA haplotype. They also show that rare predicted loss-of-function variants in CDH11 are associated with risk of recurrent pregnancy loss.

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.

Sarcoidosis is an inflammatory systemic disorder characterized by the granulomas developed in epithelioid cells in various organs. Here, the authors identify ancient endogenous retrovirus THE1B fusion transcripts that are aberrantly expressed in sarcoidosis.

A genome-wide association study highlights a variant in DOCK2, which is common in East Asian populations but rare in Europeans, as a host genetic risk factor for severe COVID-19.

Here, the authors apply novel pangenome indexes created from diverse human references to facilitate computationally efficient removal of host genetic information, preserving biological accuracy and protecting patient privacy in metagenomic sequencing analyses.

Using biobank data from over 250,000 participants, the authors present a detailed picture of regional and individual variation in the tripartite ancestral structure of modern Japanese populations and demonstrate its impact on elevated body mass index.

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.

Peripheral blood mononuclear cells from 73 Japanese patients with coronavirus disease 2019 (COVID-19) and 75 healthy controls were analyzed using single-cell transcriptomics. Combining these data with genotyping data highlights the interplay between host genetics and the immune response in modulating disease severity.

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.

Genetic mechanisms influencing COVID-19 susceptibility are not well understood. Here, the authors analyzed whole blood RNA-seq data of 465 Japanese individuals with COVID-19, highlighting thousands of fine-mapped variants affecting expression and splicing of genes, as well as the presence of COVID-19 severity-interaction eQTLs.

Private enterprises offer preimplantation genetic testing with polygenic scores to select embryos with ‘desirable’ potential. In silico simulations using biobank resources show that the selected embryo would rely substantially on the choice of polygenic score method and randomness in score construction, which raises ethical concerns.

Statistical fine-mapping of mRNA and protein quantitative trait loci in blood samples from the Japan COVID-19 Task Force sheds light on regulatory mechanisms and disease associations.

Autoimmune pulmonary alveolar proteinosis (aPAP) is a complex lung disease caused by abnormal surfactant homeostasis. Here, the authors carry out a genome-wide association study of aPAP in a Japanese cohort, finding variants in the MHC and suggesting predisposition to abnormal antibody production.

Yamamoto et al. find genetic evidence of assortative mating based on dietary habits and disease phenotypes in the Japanese population, and show that this pattern of partner choice is markedly different from its European-ancestry counterpart.

Investigating genetically correlated cancers can enhance our understanding of carcinogenesis. Here, the authors perform Pan-cancer and cross-population GWAS meta-analysis to identify novel cancer risk loci and highlight shared heritability between breast and prostate cancer.

Personal information such as genetic sex, ancestry and clinically relevant genetic variants can be recovered from human reads present in faecal metagenomic sequencing data.

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.

A global network of researchers was formed to investigate the role of human genetics in SARS-CoV-2 infection and COVID-19 severity; this paper reports 13 genome-wide significant loci and potentially actionable mechanisms in response to infection.

Naito and Inoue, et al. apply machine learning to reveal heterogeneous associations between environmental factors and diseases across polygenic risk scores. Focusing on cardiometabolic diseases shows that those with high genetic disease susceptibility may not necessarily benefit the most from the reduction of corresponding disease risk factors.