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Using multi-ancestry genome-wide association study and fine-mapping, 298 loci and 36 credible genes are identified in the aetiology of bipolar disorder.

This study used fine-mapping to analyze genetic regions associated with bipolar disorder, identifying specific risk genes and providing new insights into the biology of the condition that may guide future research and treatment approaches.

A genome-wide association study including over 76,000 individuals with schizophrenia and over 243,000 control individuals identifies common variant associations at 287 genomic loci, and further fine-mapping analyses highlight the importance of genes involved in synaptic processes.

Bando et al. perform a phase II trial of atezolizumab monotherapy following platinum-based definitive chemoradiotherapy in patients with unresectable locally advanced esophageal squamous cell carcinoma and report a complete response rate of 42%.

Anti-EGFR therapy plus doublet chemotherapy is standard of care for patients with RAS wild-type metastatic colorectal cancer (mCRC) but the role of triplet chemotherapy is unclear. Here, the authors report a randomised phase 2 trial testing the superiority of adding cetuximab (anti-EGFR) over bevacizumab (anti-VEGF) to modified FOLFOXIRI (5-FU, leucovorin, oxaliplatin and irinotecan) in patients with RAS wild-type mCRC.

Lipids are complex molecules crucial for life. The authors developed MS-DIAL 5, a tool that enhances in-depth structure elucidations and the spatial mapping of lipidome. Using advanced techniques, they uncovered new insights into the biosynthetic pathway of eye-specific phosphatidylcholines.

Clear cell renal cell carcinoma (ccRCC) usually metastasizes to the lungs. Here, the authors discover that SWI/SNF ATPase subunit SMARCA4 silencing of HLF regulates ccRCC lung metastasis by modulating the integration of collagen's mechanical cues with the actin cytoskeleton through leupaxin.

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.

Clinical manifestations in patients with systemic sclerosis (SSc) are highly heterogeneous, and identifying the root causes of clinical symptoms is challenging. Here, by performing single-cell profiling of peripheral blood from SSc patients, the authors identify distinct immune abnormalities associated with acute organ complications, including interstitial lung disease and scleroderma renal crisis.

Neural data analysis algorithms capable of tracking neuronal signals from one-photon functional imaging data longitudinally and reliably are still lacking. Here authors developed CaliAli, a tool for extracting calcium signals across multiple days. Validated with optogenetic tagging, dual-color imaging, and place cell data, CaliAli demonstrated stable neuron tracking for up to 99 days.

Neutrophils are early mediators for inflammation, but their functions in autoimmunity is still unclear. By using single cell analyses to compare patients with microscopic polyangiitis (MPA) and controls, here the authors find increased IFN-II-related neutrophils induced by IFN-γ and TNF signaling as a relapse risk marker for small vessel vasculitis.

Eukaryotic chromosomes are organized into arrays of compact domain structures called TADs. Here the authors show that a member of the Archaea, the prokaryotic domain closest to the Eukarya, uses a eukaryotic-like mechanism of chromosomal domain formation.

Here, the authors perform a multi-biome analysis in ulcerative colitis and Crohn’s disease patients from the Japanese 4D cohort, identifying intra- and trans-kingdom interactions including bacteria, phages, and fungi, providing potential candidate therapeutic targets.

The immune-checkpoint molecule TIM-3 regulates microglial homeostasis, and its microglial-specific deletion reduced cognitive impairment in a mouse model of Alzheimer’s disease.

Genome-wide association analyses of 41,917 bipolar disorder cases and 371,549 controls of European ancestry provide new insights into the etiology of this disorder and identify novel therapeutic leads and potential opportunities for drug repurposing.

Somatic mutations in ASXL1 lead to clonal hematopoiesis, and Sato et al. elucidate the molecular mechanisms by which mutated ASXL1 in hematopoietic cells drives atherosclerosis in mice.

This study uses gene expression predictors for the dorsolateral prefrontal cortex and other brain regions to perform a transcriptomic imputation analysis of schizophrenia, identifying 413 genic associations across 13 brain regions and 36 significantly enriched pathways.

In chronic myeloid leukaemia (CML), the drivers of blast crisis and resistance to tyrosine kinase inhibitors are not fully characterised. Here, the authors analyse a cohort of CML samples with genomic technologies and find that at least one driver alteration is associated with progression and worse prognosis.

The integration of human papillomavirus (HPV) drives HPV-positive head and neck squamous cell carcinoma (HPV⁺ HNSCC). Here, the authors perform genomic analysis to investigate HPV integration in patients with HPV⁺ HNSCC, identifying intratumor heterogeneity and biased distribution of HPV integration.

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.

Autoimmune vasculitis can be heterogeneous in terms of immune cell involvement. Here the authors use a single cell transcriptomics approach to characterise a group of microscopic polyangiitis patients that could be split into two groups typified by monocyte or Interferon associated gene expression.

Post-translational modifications, such as glycosylation and sialylation, are thought to confer disease modifying effects on autoimmune-associated antibodies, including anti-citrullinated protein antibodies in rheumatoid arthritis. Here the authors show that sialylation converts arthritogenic IgG into inhibitors of collagen-induced arthritis in mice.

Understanding the genomic features of dedifferentiated liposarcoma (DDLPS) is likely to uncover new options for management. Here, the authors reveal three prognostic groups, and highlight molecular markers associated with malignant transformation.

Genome-wide analysis of 3D chromatin topologies across gastric cancers suggests that Epstein–Barr virus infection may induce the epigenetic rewiring of EBV-positive tumors through human–viral chromatin interactions, a phenomenon termed ‘enhancer infestation’.

During development, astrocytes are generated from radial glia, and migrate to the cortical plate, but the process of astrocyte migration during development is not fully understood. Here the authors labelled cells derived from the cortical ventricular zone in the late stages of cortical plate development in mice, and identified a migration mode in which cells move rapidly and almost at random within the intermediate zone and the cortical plate.

Osteoclasts secrete small extracellular vesicles that stimulate osteoblasts, promoting bone formation via receptor activator of nuclear factor-kappa B ligand (RANKL), thereby linking bone formation and resorption.

MiRNAs are small RNA molecules that can regulate gene expression. Here the authors show that expression of several exosomal miRNAs are altered in patients with multiple sclerosis, and that let-7i modulates regulatory T cell homeostasis to contribute to pathogenesis.

A multi-cohort genome-wide association study of tau PET, a brain imaging-based marker of Alzheimer’s disease, identifies a CYP1B1-RMDN2 locus as associated with higher tau and faster cognitive decline. These results suggest a new genetic contribution to cerebral tau and target for Alzheimer’s disease research.

Seishi Ogawa and colleagues report an integrated genomics analysis of more than 100 clear-cell renal carcinoma samples. They analyze whole genomes or exomes, RNA sequences and DNA methylation in ∼100 paired specimens and perform SNP array-based copy number analysis for 240 specimens. They identify new recurrently mutated pathways and new associations between DNA methylation, mutations, gene expression and copy number profiles.

Here, Nishijima et al. perform a large-scale analysis of the human gut virome in the Japanese 4D cohort of 4198 deeply phenotyped individuals, revealing thousands of bacteriophage genomes, virus-bacteria interactions, and describing associations with various host and environmental factors.

At low temperatures, the orbital degrees of freedom in insulating magnets normally do not fluctuate, leaving only magnetic behaviour. Measurements now suggest that in Pr₂Zr₂O₇, it is possible to reach a quantum regime of coupled spin–orbital dynamics.

Appropriate processing of value information is essential for survival. Here the authors show that in mice, serotonergic activations originating from the median raphe nucleus facilitated aversion in a pathway-dependent manner, while silencing this pathway was rewarding.

Stratified medicine promises to tailor treatment for individual patients, however it remains a major challenge to leverage genetic risk data to aid patient stratification. Here the authors introduce an approach to stratify individuals based on the aggregated impact of their genetic risk factor profiles on tissue-specific gene expression levels, and highlight its ability to identify biologically meaningful and clinically actionable patient subgroups, supporting the notion of different patient ‘biotypes’ characterized by partially distinct disease mechanisms.

Genome-wide meta-analysis with individuals of East Asian or European ancestry identifies 176 loci associated with schizophrenia. Despite consistent genetic effects across populations, polygenic risk models trained in one population have reduced performance in the other population.