ArticleNature genetics2021
Uncovering genetic mechanisms of hypertension through multi-omic analysis of the kidney.
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Article in Nature genetics, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 50 papers, 2 of them syntheses that pooled it.
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50citing papers in PubMed, 2 pooled it
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Who cites it
50 citing papers in PubMed, 2 syntheses or guidelines pooled it.
- Brain multi-omic Mendelian randomisation to identify novel drug targets for gliomagenesis.Human molecular genetics · 2025Pooled it
- Genetics in chronic kidney disease: conclusions from a Kidney Disease: Improving Global Outcomes (KDIGO) Controversies Conference.Kidney international · 2022Guideline
- Multi-omics-driven precision medicine.iMeta · 2026Review
- Integrative genetic analysis reveals shared genetic architecture underlying coronary artery disease, CT-Defined coronary atherosclerosis, and cardiometabolic risk factors.Functional & integrative genomics · 2026Article
- Molecular systems, human noncoding sequence variants, and blood pressure.Physiological reviews · 2026Review
- Shorter kidney telomeres are associated with nephrosclerosis by an epigenetic signature.Cardiovascular research · 2026Article
- Mendelian randomization linking metabolites with enzymes reveals pathway regulation and therapeutic avenues.American journal of human genetics · 2026Article
- The genetics of hypertension.Nature reviews. Nephrology · 2026Review
- Article
- The proteogenomic landscape of the human kidney and implications for cardio-kidney-metabolic health.Nature medicine · 2025 · on this mapArticle
- Beyond Blood Pressure: Emerging Pathways and Precision Approaches in Hypertension-Induced Kidney Damage.International journal of molecular sciences · 2025Review
- Renal-Cardiac Crosstalk in the Pathogenesis and Progression of Heart Failure.Circulation research · 2025Review
- Distinct pathway-based effects of blood pressure and body mass index on cardiovascular traits: comparison of novel Mendelian randomization approaches.Genome medicine · 2025Article
- GWAS for Defining the Pathogenesis of Hypertension: Have They Delivered?Hypertension (Dallas, Tex. : 1979) · 2025Review
- 2025 Heart Disease and Stroke Statistics: A Report of US and Global Data From the American Heart Association.Circulation · 2025Review
- Kidney multiome-based genetic scorecard reveals convergent coding and regulatory variants.Science (New York, N.Y.) · 2025Article
- Transcriptome size matters for single-cell RNA-seq normalization and bulk deconvolution.Nature communications · 2025Article
- Mendelian Randomization Studies: Opening a New Window in the Study of Metabolic Diseases and Chronic Kidney Disease.Endocrine, metabolic & immune disorders drug targets · 2025Review
- Harnessing the power of genomics in hypertension: tip of the iceberg?Cambridge prisms. Precision medicine · 2025Review
- Calciprotein particle counts associate with vascular remodelling in chronic kidney disease.Cardiovascular research · 2024Article
Corrections and comments
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Authors and funding
49 authors.
James M Eales *Division of Cardiovascular Sciences, Faculty of Medicine, Biology and Health, University of Manchester, Manchester, UK.ORCID http://orcid.org/0000-0001-6238-5952
Xiao Jiang *Division of Cardiovascular Sciences, Faculty of Medicine, Biology and Health, University of Manchester, Manchester, UK.ORCID http://orcid.org/0000-0002-1442-8927
Xiaoguang Xu *Division of Cardiovascular Sciences, Faculty of Medicine, Biology and Health, University of Manchester, Manchester, UK.ORCID http://orcid.org/0000-0003-4568-1623
Sushant SalujaDivision of Cardiovascular Sciences, Faculty of Medicine, Biology and Health, University of Manchester, Manchester, UK.
Artur AkbarovDivision of Cardiovascular Sciences, Faculty of Medicine, Biology and Health, University of Manchester, Manchester, UK.
Eddie Cano-GamezDepartment of Human Genetics, Wellcome Sanger Institute, Cambridge, UK.
Michelle T McNultyDivision of Nephrology, Boston Children's Hospital, Boston, MA, USA.
Christopher FinanInstitute of Cardiovascular Science, University College London, London, UK.ORCID http://orcid.org/0000-0002-3319-1937
Hui GuoCentre for Biostatistics, School of Health Sciences, Faculty of Medicine, Biology and Health, University of Manchester, Manchester, UK.ORCID http://orcid.org/0000-0003-0282-6933
Wojciech WystrychowskiDepartment of General, Vascular and Transplant Surgery, Medical University of Silesia, Katowice, Poland.
Monika SzulinskaDepartment of Obesity, Metabolic Disorders Treatment and Clinical Dietetics, Karol Marcinkowski University of Medical Sciences, Poznan, Poland.ORCID http://orcid.org/0000-0002-1163-0919
Huw B ThomasDivision of Evolution and Genomic Sciences, Faculty of Medicine, Biology and Health, University of Manchester, Manchester, UK.ORCID http://orcid.org/0000-0001-9626-9706
Sanjeev PramanikDivision of Cardiovascular Sciences, Faculty of Medicine, Biology and Health, University of Manchester, Manchester, UK.ORCID http://orcid.org/0000-0003-2317-3628
Sandesh ChopadeInstitute of Cardiovascular Science, University College London, London, UK.
Priscilla R PrestesHealth Innovation and Transformation Centre, School of Science, Psychology and Sport, Federation University Australia, Ballarat, Victoria, Australia.ORCID http://orcid.org/0000-0002-9034-6595
Ingrid WiseAustralian Institute of Tropical Health & Medicine, James Cook University, Cairns, Queensland, Australia.
Evangelos EvangelouDepartment of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, UK.ORCID http://orcid.org/0000-0002-5488-2999
Mahan SalehiDivision of Cardiovascular Sciences, Faculty of Medicine, Biology and Health, University of Manchester, Manchester, UK.ORCID http://orcid.org/0000-0002-4064-4762
Yusif ShakantiDivision of Cardiovascular Sciences, Faculty of Medicine, Biology and Health, University of Manchester, Manchester, UK.
Mikael EkholmDivision of Cardiovascular Sciences, Faculty of Medicine, Biology and Health, University of Manchester, Manchester, UK.
Matthew DenniffDepartment of Cardiovascular Sciences, University of Leicester, Leicester, UK.
Alicja NazgiewiczDivision of Cardiovascular Sciences, Faculty of Medicine, Biology and Health, University of Manchester, Manchester, UK.
Felix EichingerDepartment of Medicine, University of Michigan, Ann Arbor, MI, USA.
Bradley GodfreyDepartment of Urology and Uro-oncology, Karol Marcinkowski University of Medical Sciences, Poznan, Poland.
Andrzej AntczakDepartment of Urology and Uro-oncology, Karol Marcinkowski University of Medical Sciences, Poznan, Poland.
Maciej GlydaDepartment of Transplantology and General Surgery Poznan, Collegium Medicum, Nicolaus Copernicus University, Bydgoszcz, Poland.
Robert KrólDepartment of General, Vascular and Transplant Surgery, Medical University of Silesia, Katowice, Poland.
Stephen EyreDivision of Musculoskeletal and Dermatological Sciences, Faculty of Medicine, Biology and Health, University of Manchester, Manchester, UK.ORCID http://orcid.org/0000-0002-1251-6974
Jason BrownDivision of Research and Innovation, Manchester University NHS Foundation Trust, Manchester, UK.
Carlo BerzuiniCentre for Biostatistics, School of Health Sciences, Faculty of Medicine, Biology and Health, University of Manchester, Manchester, UK.ORCID http://orcid.org/0000-0001-6056-0489
John BowesDivision of Musculoskeletal and Dermatological Sciences, Faculty of Medicine, Biology and Health, University of Manchester, Manchester, UK.ORCID http://orcid.org/0000-0003-4659-031X
Mark CaulfieldWilliam Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, UK.ORCID http://orcid.org/0000-0001-9295-3594
Ewa Zukowska-SzczechowskaDepartment of Health Care, Silesian Medical College, Katowice, Poland.
Joanna ZywiecDepartment of Internal Medicine, Diabetology and Nephrology, Zabrze, Medical University of Silesia, Katowice, Poland.
Pawel BogdanskiDepartment of Obesity, Metabolic Disorders Treatment and Clinical Dietetics, Karol Marcinkowski University of Medical Sciences, Poznan, Poland.
Matthias KretzlerDepartment of Medicine, University of Michigan, Ann Arbor, MI, USA.
Adrian S WoolfDivision of Cell Matrix Biology and Regenerative Medicine, Faculty of Biology, Medicine and Health, University of Manchester, Manchester, UK.ORCID http://orcid.org/0000-0001-5541-1358
David TalaveraDivision of Cardiovascular Sciences, Faculty of Medicine, Biology and Health, University of Manchester, Manchester, UK.ORCID http://orcid.org/0000-0002-8820-3931
Bernard KeavneyDivision of Cardiovascular Sciences, Faculty of Medicine, Biology and Health, University of Manchester, Manchester, UK.ORCID http://orcid.org/0000-0001-9573-0812
Pasquale MaffiaInstitute of Infection, Immunity and Inflammation, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, UK.ORCID http://orcid.org/0000-0003-3926-4225
Tomasz J GuzikInstitute of Cardiovascular and Medical Sciences, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, UK.ORCID http://orcid.org/0000-0002-5039-7849
Raymond T O'KeefeDivision of Evolution and Genomic Sciences, Faculty of Medicine, Biology and Health, University of Manchester, Manchester, UK.ORCID http://orcid.org/0000-0001-8764-1289
Gosia TrynkaDepartment of Human Genetics, Wellcome Sanger Institute, Cambridge, UK.ORCID http://orcid.org/0000-0002-6955-9529
Nilesh J SamaniDepartment of Cardiovascular Sciences, University of Leicester, Leicester, UK.
Aroon HingoraniInstitute of Cardiovascular Science, University College London, London, UK.ORCID http://orcid.org/0000-0001-8365-0081
Matthew G SampsonDivision of Nephrology, Boston Children's Hospital, Boston, MA, USA.ORCID http://orcid.org/0000-0001-9560-076X
Andrew P MorrisDivision of Musculoskeletal and Dermatological Sciences, Faculty of Medicine, Biology and Health, University of Manchester, Manchester, UK.
Fadi J CharcharHealth Innovation and Transformation Centre, School of Science, Psychology and Sport, Federation University Australia, Ballarat, Victoria, Australia.ORCID http://orcid.org/0000-0002-6164-9941
Maciej TomaszewskiDivision of Cardiovascular Sciences, Faculty of Medicine, Biology and Health, University of Manchester, Manchester, UK. maciej.tomaszewski@manchester.ac.uk.ORCID http://orcid.org/0000-0001-8215-6567
Funding
Training Program in Clinical & Translationa Research in Human Glomerular DiseaseU54DK083912 · NIDDK · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI HOLZMAN, LAWRENCE B. · 2009 to 2023
$20.3MWhole Genome Sequencing for Nephrotic Syndrome DiscoveryR01DK119380 · NIDDK · BOSTON CHILDREN'S HOSPITAL · PI Dongwon Lee, MATTHEW Gordon SAMPSON · 2019 to 2026
$3.7MAPOL1 - associated nephropathy from human-derived, intrarenal perspectiveR01DK108805 · NIDDK · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI MATTHEW Gordon SAMPSON, Simone Sanna-Cherchi · 2016 to 2026
$3.4MGenetics of kidney disease in diverse populationsR01DK117445 · NIDDK · UNIV OF NORTH CAROLINA CHAPEL HILL · PI FRANCESCHINI, NORA · 2018 to 2022
$2.7MBritish Heart Foundation CH/13/2/30154British Heart Foundation PG/17/35/33001British Heart Foundation PG/19/16/34270British Heart Foundation PG/19/84/34771Medical Research Council G9521010Medical Research Council MR/R010900/1NIDDK NIH HHS R01 DK108805NIDDK NIH HHS R01 DK117445NIDDK NIH HHS R01 DK119380NIDDK NIH HHS U54 DK083912Wellcome Trust 203141/Z/16/ZWellcome Trust WT206194
Abstract
The kidney is an organ of key relevance to blood pressure (BP) regulation, hypertension and antihypertensive treatment. However, genetically mediated renal mechanisms underlying susceptibility to hypertension remain poorly understood. We integrated genotype, gene expression, alternative splicing and DNA methylation profiles of up to 430 human kidneys to characterize the effects of BP index variants from genome-wide association studies (GWASs) on renal transcriptome and epigenome. We uncovered kidney targets for 479 (58.3%) BP-GWAS variants and paired 49 BP-GWAS kidney genes with 210 licensed drugs. Our colocalization and Mendelian randomization analyses identified 179 unique kidney genes with evidence of putatively causal effects on BP. Through Mendelian randomization, we also uncovered effects of BP on renal outcomes commonly affecting patients with hypertension. Collectively, our studies identified genetic variants, kidney genes, molecular mechanisms and biological pathways of key relevance to the genetic regulation of BP and inherited susceptibility to hypertension.
Indexed as
Genetic Predisposition to DiseaseGenomicsAlternative SplicingBlood PressureDNA MethylationGenetic VariationGenome-Wide Association StudyHumansHypertensionKidneyMendelian Randomization AnalysisPolymorphism, Single NucleotideQuantitative Trait Loci
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PMID
33958779What OpenQuestion holds
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.