ArticleGenome biology2023
Transcriptome- and proteome-wide association studies nominate determinants of kidney function and damage.
Article in Genome biology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers, 1 of them a synthesis that pooled it.
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Who cites it
20 citing papers in PubMed, 1 synthesis or guideline pooled it, 29 citations in OpenAlex.
- Pooled it
- Integrative Proteogenomics and Single-Cell Transcriptomics Prioritize Candidate Causal Proteins and Therapeutic Targets in Age-Related Macular Degeneration.International journal of molecular sciences · 2026Article
- Protein mediators of chronic kidney disease in Type 2 diabetes: A mendelian randomization study.PLoS medicine · 2026Article
- Proteogenomics in human populations.Nature reviews. Genetics · 2026Review
- AI-based multimodal integration of genomics and electronic health records.Nature reviews. Genetics · 2026Review
- ELF3 links kidney function GWAS loci to maladaptive epithelial inflammation.Science advances · 2026Article
- Decoding Complex Traits in Goats Through Genome-Wide Association Studies: Progress, Challenges, and Perspectives.International journal of molecular sciences · 2026Review
- Identification of novel therapeutic targets for diabetic neuropathy through integrated proteomics and transcriptomics approaches.World journal of diabetes · 2025Article
- The proteogenomic landscape of the human kidney and implications for cardio-kidney-metabolic health.Nature medicine · 2025 · on this mapArticle
- Integrative multi-omics approaches identify molecular pathways and improve Alzheimer's disease risk prediction.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Article
- Integrative Proteome- and Phenome-Wide Assessment Uncovers Causal Protein Drivers and Drug Targets for Heterogeneous Kidney Diseases.medRxiv : the preprint server for health sciences · 2025Article
- Article
- Genetic prioritisation of candidate drug targets for glaucoma through multi-trait and multi-omics integration.Eye and vision (London, England) · 2025Article
- Renal-Cardiac Crosstalk in the Pathogenesis and Progression of Heart Failure.Circulation research · 2025Review
- Integrative analysis of transcriptome and proteome wide association studies prioritized functional genes for obesity.Human genetics · 2025Article
- Article
- Identification of novel therapeutic targets for chronic kidney disease and kidney function by integrating multi-omics proteome with transcriptome.Genome medicine · 2024Article
- Article
- Genetic imputation of kidney transcriptome, proteome and multi-omics illuminates new blood pressure and hypertension targets.Nature communications · 2024Article
- Brief research report: WGCNA-driven identification of histone modification genes as potential biomarkers in AQP4-Associated optic neuritis.Frontiers in genetics · 2024Article
Corrections and comments
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Authors and funding
13 authors at 5 institutions in 1 country.
Funding
Abstract
backgroundThe pathophysiological causes of kidney disease are not fully understood. Here we show that the integration of genome-wide genetic, transcriptomic, and proteomic association studies can nominate causal determinants of kidney function and damage.
resultsThrough transcriptome-wide association studies (TWAS) in kidney cortex, kidney tubule, liver, and whole blood and proteome-wide association studies (PWAS) in plasma, we assess for effects of 12,893 genes and 1342 proteins on kidney filtration (glomerular filtration rate (GFR) estimated by creatinine; GFR estimated by cystatin C; and blood urea nitrogen) and kidney damage (albuminuria). We find 1561 associations distributed among 260 genomic regions that are supported as putatively causal. We then prioritize 153 of these genomic regions using additional colocalization analyses. Our genome-wide findings are supported by existing knowledge (animal models for MANBA, DACH1, SH3YL1, INHBB), exceed the underlying GWAS signals (28 region-trait combinations without significant GWAS hit), identify independent gene/protein-trait associations within the same genomic region (INHBC, SPRYD4), nominate tissues underlying the associations (tubule expression of NRBP1), and distinguish markers of kidney filtration from those with a role in creatinine and cystatin C metabolism. Furthermore, we follow up on members of the TGF-beta superfamily of proteins and find a prognostic value of INHBC for kidney disease progression even after adjustment for measured glomerular filtration rate (GFR).
conclusionIn summary, this study combines multimodal, genome-wide association studies to generate a catalog of putatively causal target genes and proteins relevant to kidney function and damage which can guide follow-up studies in physiology, basic science, and clinical medicine.
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Registered trials
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