Cell Genomics (Jan 2024)
Genome-wide study investigating effector genes and polygenic prediction for kidney function in persons with ancestry from Africa and the Americas
- Odessica Hughes,
- Amy R. Bentley,
- Charles E. Breeze,
- Francois Aguet,
- Xiaoguang Xu,
- Girish Nadkarni,
- Quan Sun,
- Bridget M. Lin,
- Thomas Gilliland,
- Mariah C. Meyer,
- Jiawen Du,
- Laura M. Raffield,
- Holly Kramer,
- Robert W. Morton,
- Mateus H. Gouveia,
- Elizabeth G. Atkinson,
- Adan Valladares-Salgado,
- Niels Wacher-Rodarte,
- Nicole D. Dueker,
- Xiuqing Guo,
- Yang Hai,
- Adebowale Adeyemo,
- Lyle G. Best,
- Jianwen Cai,
- Guanjie Chen,
- Michael Chong,
- Ayo Doumatey,
- James Eales,
- Mark O. Goodarzi,
- Eli Ipp,
- Marguerite Ryan Irvin,
- Minzhi Jiang,
- Alana C. Jones,
- Charles Kooperberg,
- Jose E. Krieger,
- Ethan M. Lange,
- Matthew B. Lanktree,
- James P. Lash,
- Paulo A. Lotufo,
- Ruth J.F. Loos,
- Vy Thi Ha My,
- Jesús Peralta-Romero,
- Lihong Qi,
- Leslie J. Raffel,
- Stephen S. Rich,
- Erik J. Rodriquez,
- Eduardo Tarazona-Santos,
- Kent D. Taylor,
- Jason G. Umans,
- Jia Wen,
- Bessie A. Young,
- Zhi Yu,
- Ying Zhang,
- Yii-Der Ida Chen,
- Tanja Rundek,
- Jerome I. Rotter,
- Miguel Cruz,
- Myriam Fornage,
- Maria Fernanda Lima-Costa,
- Alexandre C. Pereira,
- Guillaume Paré,
- Pradeep Natarajan,
- Shelley A. Cole,
- April P. Carson,
- Leslie A. Lange,
- Yun Li,
- Eliseo J. Perez-Stable,
- Ron Do,
- Fadi J. Charchar,
- Maciej Tomaszewski,
- Josyf C. Mychaleckyj,
- Charles Rotimi,
- Andrew P. Morris,
- Nora Franceschini
Affiliations
- Odessica Hughes
- Centre for Genetics and Genomics Versus Arthritis, Centre for Musculoskeletal Research, The University of Manchester, Manchester, UK
- Amy R. Bentley
- Center for Research on Genomics and Global Health, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USA
- Charles E. Breeze
- Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Department Health and Human Services, Bethesda, MD, USA; UCL Cancer Institute, University College London, London, UK
- Francois Aguet
- The Broad Institute of MIT and Harvard, Cambridge, MA, USA
- Xiaoguang Xu
- Division of Cardiovascular Sciences, Faculty of Biology, Medicine, and Health, The University of Manchester, Manchester, UK
- Girish Nadkarni
- The Charles Bronfman Institute of Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA
- Quan Sun
- Department of Biostatistics, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
- Bridget M. Lin
- Department of Biostatistics, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
- Thomas Gilliland
- Cardiovascular Research Center and Center for Genomic Medicine, Massachusetts General Hospital, Boston, MA, USA; Program in Medical and Population Genetics and the Cardiovascular Disease Initiative, Broad Institute, Cambridge, MA, USA; Department of Medicine, Harvard Medical School, Boston, MA, USA
- Mariah C. Meyer
- Department of Biomedical Informatics, University of Colorado Anschutz Medical Campus, Aurora, CO, USA
- Jiawen Du
- Department of Biostatistics, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
- Laura M. Raffield
- Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
- Holly Kramer
- Division of Nephrology and Hypertension, Loyola University Chicago, Maywood, IL, USA
- Robert W. Morton
- Population Health Research Institute, Hamilton, ON, Canada; Department of Pathology and Molecular Medicine, McMaster University, Hamilton, ON, Canada
- Mateus H. Gouveia
- Center for Research on Genomics and Global Health, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USA
- Elizabeth G. Atkinson
- Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA
- Adan Valladares-Salgado
- Unidad de Investigación Médica en Bioquímica, Hospital de Especialidades, Centro Médico Nacional Siglo XXI, Instituto Mexicano del Seguro Social, Mexico City, Mexico
- Niels Wacher-Rodarte
- Unidad de Investigación Médica en Epidemiologia Clinica, Hospital de Especialidades, Centro Médico Nacional Siglo XXI, Instituto Mexicano del Seguro Social, Mexico City, Mexico
- Nicole D. Dueker
- John P Hussman Institute for Human Genomics, University of Miami Miller School of Medicine, Miami, FL, USA
- Xiuqing Guo
- The Institute for Translational Genomics and Population Sciences, Department of Pediatrics, The Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center, Torrance, CA USA
- Yang Hai
- The Institute for Translational Genomics and Population Sciences, Department of Pediatrics, The Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center, Torrance, CA USA
- Adebowale Adeyemo
- Center for Research on Genomics and Global Health, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USA
- Lyle G. Best
- Missouri Breaks Industries Research Inc., Eagle Butte, SD, USA
- Jianwen Cai
- Department of Biostatistics, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
- Guanjie Chen
- Center for Research on Genomics and Global Health, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USA
- Michael Chong
- Population Health Research Institute, Hamilton, ON, Canada; Department of Pathology and Molecular Medicine, McMaster University, Hamilton, ON, Canada
- Ayo Doumatey
- Center for Research on Genomics and Global Health, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USA
- James Eales
- Division of Cardiovascular Sciences, Faculty of Biology, Medicine, and Health, The University of Manchester, Manchester, UK
- Mark O. Goodarzi
- Division of Endocrinology, Diabetes, and Metabolism, Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, CA, USA
- Eli Ipp
- Division of Endocrinology and Metabolism, Department of Medicine, The Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center, Torrance, CA, USA
- Marguerite Ryan Irvin
- Department of Epidemiology, University of Alabama at Birmingham, Birmingham, AL, USA
- Minzhi Jiang
- Department of Applied Physical Sciences, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
- Alana C. Jones
- Department of Epidemiology, University of Alabama at Birmingham, Birmingham, AL, USA
- Charles Kooperberg
- Division of Public Health Sciences, Fred Hutchinson Cancer Center, Seattle, WA, USA
- Jose E. Krieger
- Laboratório de Genética e Cardiologia Molecular do Instituto do Coração do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil
- Ethan M. Lange
- Department of Biomedical Informatics, University of Colorado Anschutz Medical Campus, Aurora, CO, USA
- Matthew B. Lanktree
- Division of Nephrology, Department of Medicine, McMaster University, Hamilton, ON, Canada
- James P. Lash
- Division of Nephrology, Department of Medicine, University of Illinois, Chicago, IL, USA
- Paulo A. Lotufo
- Center for Clinical and Epidemiological Research, Hospital Universitário, Universidade de São Paulo (USP), São Paulo, Brazil
- Ruth J.F. Loos
- The Charles Bronfman Institute of Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
- Vy Thi Ha My
- The Charles Bronfman Institute of Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA
- Jesús Peralta-Romero
- Unidad de Investigación Médica en Bioquímica, Hospital de Especialidades, Centro Médico Nacional Siglo XXI, Instituto Mexicano del Seguro Social, Mexico City, Mexico
- Lihong Qi
- Department of Public Health Sciences, School of Medicine, University of California Davis, Davis, CA, USA
- Leslie J. Raffel
- Department of Pediatrics, Genetic and Genomic Medicine, University of California, Irvine, Irvine, CA, USA
- Stephen S. Rich
- Center for Public Health Genomics, University of Virginia, Charlottesville, VA, USA
- Erik J. Rodriquez
- Division of Intramural Research, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, USA
- Eduardo Tarazona-Santos
- Departamento de Genética, Ecologia e Evolução, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil
- Kent D. Taylor
- The Institute for Translational Genomics and Population Sciences, Department of Pediatrics, The Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center, Torrance, CA USA
- Jason G. Umans
- MedStar Health Research Institute, Hyattsville MD and Georgetown-Howard Universities Center for Clinical and Translational Science, Washington, DC, USA
- Jia Wen
- Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
- Bessie A. Young
- University of Washington School of Medicine, Seattle, WA, USA; Office of Healthcare Equity, UW Justice, Equity, Diversity, and Inclusion Center for Transformational Research (UW JEDI-CTR), University of Washington, Seattle, WA, USA; Division of Nephrology, Department of Medicine, University of Washington, Seattle, WA, USA; Kidney Research Institute, Department of Medicine, University of Washington, Seattle, WA, USA
- Zhi Yu
- Cardiovascular Research Center and Center for Genomic Medicine, Massachusetts General Hospital, Boston, MA, USA; Program in Medical and Population Genetics and the Cardiovascular Disease Initiative, Broad Institute, Cambridge, MA, USA
- Ying Zhang
- Center for American Indian Health Research, Department of Biostatistics and Epidemiology, Hudson College of Public Health, The University of Oklahoma Health Sciences Center, Oklahoma, OK, USA
- Yii-Der Ida Chen
- The Institute for Translational Genomics and Population Sciences, Department of Pediatrics, The Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center, Torrance, CA USA
- Tanja Rundek
- Department of Neurology, Epidemiology and Public Health, Miller School of Medicine, University of Miami, Miami, FL, USA
- Jerome I. Rotter
- The Institute for Translational Genomics and Population Sciences, Department of Pediatrics, The Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center, Torrance, CA USA
- Miguel Cruz
- Unidad de Investigación Médica en Bioquímica, Hospital de Especialidades, Centro Médico Nacional Siglo XXI, Instituto Mexicano del Seguro Social, Mexico City, Mexico
- Myriam Fornage
- Brown Foundation Institute of Molecular Medicine, Houston, TX, USA
- Maria Fernanda Lima-Costa
- Instituto René Rachou, Fundação Oswaldo Cruz, Belo Horizonte, Brazil
- Alexandre C. Pereira
- Laboratório de Genética e Cardiologia Molecular do Instituto do Coração do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil; Aging Division, Brigham Women’s Hospital, Department of Medicine, Harvard Medical School, Boston, MA, USA
- Guillaume Paré
- Population Health Research Institute, Hamilton, ON, Canada; Department of Pathology and Molecular Medicine, McMaster University, Hamilton, ON, Canada
- Pradeep Natarajan
- Cardiovascular Research Center and Center for Genomic Medicine, Massachusetts General Hospital, Boston, MA, USA; Program in Medical and Population Genetics and the Cardiovascular Disease Initiative, Broad Institute, Cambridge, MA, USA; Department of Medicine, Harvard Medical School, Boston, MA, USA
- Shelley A. Cole
- Texas Biomedical Research Institute, San Antonio, TX, USA
- April P. Carson
- Department of Medicine, University of Mississippi Medical Center, Jackson, MS, USA
- Leslie A. Lange
- Department of Biomedical Informatics, University of Colorado Anschutz Medical Campus, Aurora, CO, USA
- Yun Li
- Department of Biostatistics, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
- Eliseo J. Perez-Stable
- National Institute on Minority Health and Health Disparities, National Institutes of Health, Bethesda, MD, USA
- Ron Do
- The Charles Bronfman Institute of Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA
- Fadi J. Charchar
- School of Science, Psychology and Sport, Federation University, Ballarat, VIC, Australia; Department of Cardiovascular Sciences, University of Leicester, Leicester, UK; Department of Physiology, University of Melbourne, Melbourne, VIC, Australia
- Maciej Tomaszewski
- Division of Cardiovascular Sciences, Faculty of Biology, Medicine, and Health, The University of Manchester, Manchester, UK; Manchester Royal Infirmary, Manchester University NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester, UK
- Josyf C. Mychaleckyj
- Department of Public Health Sciences, School of Medicine, University of California Davis, Davis, CA, USA
- Charles Rotimi
- Center for Research on Genomics and Global Health, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USA
- Andrew P. Morris
- Centre for Genetics and Genomics Versus Arthritis, Centre for Musculoskeletal Research, The University of Manchester, Manchester, UK; Corresponding author
- Nora Franceschini
- Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA; Corresponding author
- Journal volume & issue
-
Vol. 4,
no. 1
p. 100468
Abstract
Summary: Chronic kidney disease is a leading cause of death and disability globally and impacts individuals of African ancestry (AFR) or with ancestry in the Americas (AMS) who are under-represented in genome-wide association studies (GWASs) of kidney function. To address this bias, we conducted a large meta-analysis of GWASs of estimated glomerular filtration rate (eGFR) in 145,732 AFR and AMS individuals. We identified 41 loci at genome-wide significance (p < 5 × 10−8), of which two have not been previously reported in any ancestry group. We integrated fine-mapped loci with epigenomic and transcriptomic resources to highlight potential effector genes relevant to kidney physiology and disease, and reveal key regulatory elements and pathways involved in renal function and development. We demonstrate the varying but increased predictive power offered by a multi-ancestry polygenic score for eGFR and highlight the importance of population diversity in GWASs and multi-omics resources to enhance opportunities for clinical translation for all.
