Kidney dysfunction is a major cause of mortality, but its genetic architecture remains elusive. In this study, we conducted a multiancestry genome-wide association study in 2.2 million individuals and identified 1026 (97 previously unknown) independent loci. Ancestry-specific analysis indicated an attenuation of newly identified signals on common variants in European ancestry populations and the power of population diversity for further discoveries. We defined genotype effects on allele-specific gene expression and regulatory circuitries in more than 700 human kidneys and 237,000 cells. We found 1363 coding variants disrupting 782 genes, with 601 genes also targeted by regulatory variants and convergence in 161 genes. Integrating 32 types of genetic information, we present the "Kidney Disease Genetic Scorecard" for prioritizing potentially causal genes, cell types, and druggable targets for kidney disease.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1126/science.adp4753 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
The CREscendoing promise of HDAC targeting to limit atherosclerosis.
Immunity
March 2025
Department of Laboratory Medicine, Medical University of Vienna, Vienna, Austria. Electronic address:
The factors that modulate the inflammatory response in atherosclerosis are not well defined. In this issue of Immunity, Asare et al. examine the impact of a cis-regulatory element (CRE) that controls expression of HDAC9 and find that HDAC9-mediated deacetylation of NLRP3 might be the mechanism by which genetic variants in this conserved CRE influence the inflammation associated with human atherosclerosis.
View Article and Find Full Text PDFA human histidyl-tRNA synthetase splice variant therapeutic targets NRP2 to resolve lung inflammation and fibrosis.
Sci Transl Med
March 2025
Department of Molecular Medicine, Scripps Research Institute, La Jolla, CA 92037, USA.
Interstitial lung disease (ILD) consists of a group of immune-mediated disorders that can cause inflammation and progressive fibrosis of the lungs, representing an area of unmet medical need given the lack of disease-modifying therapies and toxicities associated with current treatment options. Tissue-specific splice variants (SVs) of human aminoacyl-tRNA synthetases (aaRSs) are catalytic nulls thought to confer regulatory functions. One example from human histidyl-tRNA synthetase (HARS), termed HARS because the splicing event resulted in a protein encompassing the WHEP-TRS domain of HARS (a structurally conserved domain found in multiple aaRSs), is enriched in human lung and up-regulated by inflammatory cytokines in lung and immune cells.
View Article and Find Full Text PDFIntegrated functional genomic analysis identifies regulatory variants underlying a major QTL for disease resistance in European sea bass.
BMC Biol
March 2025
The Roslin Institute and Royal (Dick), University of Edinburgh, Edinburgh, EH25 9RG, UK.
Background: Viral nervous necrosis (VNN) is an important viral disease threatening global aquaculture sustainability and affecting over 50 farmed and ecologically important fish species. A major QTL for resistance to VNN has been previously detected in European sea bass, but the underlying causal gene(s) and mutation(s) remain unknown. To identify the mechanisms and genetic factors underpinning resistance to VNN in European sea bass, we employed integrative analyses of multiple functional genomics assays in European sea bass.
View Article and Find Full Text PDFHOXB13 in cancer development: molecular mechanisms and clinical implications.
Front Med
March 2025
Department of Urology, Urologic Surgery Center, Xinqiao Hospital, Third Military Medical University (Army Medical University), Chongqing, 400037, China.
The transcription factor HOXB13 plays crucial roles in cancer development. HOXB13 is abnormally expressed in most cancers, which makes it a valuable therapeutic target for cancer therapy. The level of HOXB13 differs significantly between healthy and cancer tissues, which indicates that the level of HOXB13 is closely related to carcinogenesis.
View Article and Find Full Text PDFImplication of ribosomal protein in abiotic and biotic stress.
Planta
March 2025
Department of Chemistry, Biochemistry and Physics and Groupe de Recherche en Biologie Végétale, Université du Québec À Trois-Rivières, Trois-Rivières, Québec, G9A 5H9, Canada.
This review article explores the intricate role, and regulation of ribosomal protein in response to stress, particularly emphasizing their pivotal role to ameliorate abiotic and biotic stress conditions in crop plants. Plants must coordinate ribosomes production to balance cellular protein synthesis in response to environmental variations and pathogens invasion. Over the past decade, research has revealed ribosome subgroups respond to adverse conditions, suggesting that this tight coordination may be grounded in the induction of ribosome variants resulting in differential translation outcomes.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!