Genome-wide study investigating effector genes and polygenic prediction for kidney function in persons with ancestry from Africa and the Americas
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 l...
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| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2024-01-01
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| Series: | Cell Genomics |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2666979X23003129 |
| _version_ | 1827383107628564480 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Odessica Hughes |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-08T14:35:24Z |
| format | Article |
| id | doaj.art-975974e930614de28f7b1b95b70b9859 |
| institution | Directory Open Access Journal |
| issn | 2666-979X |
| language | English |
| last_indexed | 2024-03-08T14:35:24Z |
| publishDate | 2024-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Genomics |
| spelling | doaj.art-975974e930614de28f7b1b95b70b98592024-01-12T04:57:45ZengElsevierCell Genomics2666-979X2024-01-0141100468Genome-wide study investigating effector genes and polygenic prediction for kidney function in persons with ancestry from Africa and the AmericasOdessica Hughes0Amy R. Bentley1Charles E. Breeze2Francois Aguet3Xiaoguang Xu4Girish Nadkarni5Quan Sun6Bridget M. Lin7Thomas Gilliland8Mariah C. Meyer9Jiawen Du10Laura M. Raffield11Holly Kramer12Robert W. Morton13Mateus H. Gouveia14Elizabeth G. Atkinson15Adan Valladares-Salgado16Niels Wacher-Rodarte17Nicole D. Dueker18Xiuqing Guo19Yang Hai20Adebowale Adeyemo21Lyle G. Best22Jianwen Cai23Guanjie Chen24Michael Chong25Ayo Doumatey26James Eales27Mark O. Goodarzi28Eli Ipp29Marguerite Ryan Irvin30Minzhi Jiang31Alana C. Jones32Charles Kooperberg33Jose E. Krieger34Ethan M. Lange35Matthew B. Lanktree36James P. Lash37Paulo A. Lotufo38Ruth J.F. Loos39Vy Thi Ha My40Jesús Peralta-Romero41Lihong Qi42Leslie J. Raffel43Stephen S. Rich44Erik J. Rodriquez45Eduardo Tarazona-Santos46Kent D. Taylor47Jason G. Umans48Jia Wen49Bessie A. Young50Zhi Yu51Ying Zhang52Yii-Der Ida Chen53Tanja Rundek54Jerome I. Rotter55Miguel Cruz56Myriam Fornage57Maria Fernanda Lima-Costa58Alexandre C. Pereira59Guillaume Paré60Pradeep Natarajan61Shelley A. Cole62April P. Carson63Leslie A. Lange64Yun Li65Eliseo J. Perez-Stable66Ron Do67Fadi J. Charchar68Maciej Tomaszewski69Josyf C. Mychaleckyj70Charles Rotimi71Andrew P. Morris72Nora Franceschini73Centre for Genetics and Genomics Versus Arthritis, Centre for Musculoskeletal Research, The University of Manchester, Manchester, UKCenter for Research on Genomics and Global Health, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USADivision 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, UKThe Broad Institute of MIT and Harvard, Cambridge, MA, USADivision of Cardiovascular Sciences, Faculty of Biology, Medicine, and Health, The University of Manchester, Manchester, UKThe Charles Bronfman Institute of Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USADepartment of Biostatistics, University of North Carolina at Chapel Hill, Chapel Hill, NC, USADepartment of Biostatistics, University of North Carolina at Chapel Hill, Chapel Hill, NC, USACardiovascular 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, USADepartment of Biomedical Informatics, University of Colorado Anschutz Medical Campus, Aurora, CO, USADepartment of Biostatistics, University of North Carolina at Chapel Hill, Chapel Hill, NC, USADepartment of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, NC, USADivision of Nephrology and Hypertension, Loyola University Chicago, Maywood, IL, USAPopulation Health Research Institute, Hamilton, ON, Canada; Department of Pathology and Molecular Medicine, McMaster University, Hamilton, ON, CanadaCenter for Research on Genomics and Global Health, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USADepartment of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USAUnidad de Investigación Médica en Bioquímica, Hospital de Especialidades, Centro Médico Nacional Siglo XXI, Instituto Mexicano del Seguro Social, Mexico City, MexicoUnidad de Investigación Médica en Epidemiologia Clinica, Hospital de Especialidades, Centro Médico Nacional Siglo XXI, Instituto Mexicano del Seguro Social, Mexico City, MexicoJohn P Hussman Institute for Human Genomics, University of Miami Miller School of Medicine, Miami, FL, USAThe Institute for Translational Genomics and Population Sciences, Department of Pediatrics, The Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center, Torrance, CA USAThe Institute for Translational Genomics and Population Sciences, Department of Pediatrics, The Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center, Torrance, CA USACenter for Research on Genomics and Global Health, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USAMissouri Breaks Industries Research Inc., Eagle Butte, SD, USADepartment of Biostatistics, University of North Carolina at Chapel Hill, Chapel Hill, NC, USACenter for Research on Genomics and Global Health, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USAPopulation Health Research Institute, Hamilton, ON, Canada; Department of Pathology and Molecular Medicine, McMaster University, Hamilton, ON, CanadaCenter for Research on Genomics and Global Health, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USADivision of Cardiovascular Sciences, Faculty of Biology, Medicine, and Health, The University of Manchester, Manchester, UKDivision of Endocrinology, Diabetes, and Metabolism, Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, CA, USADivision of Endocrinology and Metabolism, Department of Medicine, The Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center, Torrance, CA, USADepartment of Epidemiology, University of Alabama at Birmingham, Birmingham, AL, USADepartment of Applied Physical Sciences, University of North Carolina at Chapel Hill, Chapel Hill, NC, USADepartment of Epidemiology, University of Alabama at Birmingham, Birmingham, AL, USADivision of Public Health Sciences, Fred Hutchinson Cancer Center, Seattle, WA, USALaboratório de Genética e Cardiologia Molecular do Instituto do Coração do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, São Paulo, BrazilDepartment of Biomedical Informatics, University of Colorado Anschutz Medical Campus, Aurora, CO, USADivision of Nephrology, Department of Medicine, McMaster University, Hamilton, ON, CanadaDivision of Nephrology, Department of Medicine, University of Illinois, Chicago, IL, USACenter for Clinical and Epidemiological Research, Hospital Universitário, Universidade de São Paulo (USP), São Paulo, BrazilThe 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, DenmarkThe Charles Bronfman Institute of Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USAUnidad de Investigación Médica en Bioquímica, Hospital de Especialidades, Centro Médico Nacional Siglo XXI, Instituto Mexicano del Seguro Social, Mexico City, MexicoDepartment of Public Health Sciences, School of Medicine, University of California Davis, Davis, CA, USADepartment of Pediatrics, Genetic and Genomic Medicine, University of California, Irvine, Irvine, CA, USACenter for Public Health Genomics, University of Virginia, Charlottesville, VA, USADivision of Intramural Research, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, USADepartamento de Genética, Ecologia e Evolução, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, BrazilThe Institute for Translational Genomics and Population Sciences, Department of Pediatrics, The Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center, Torrance, CA USAMedStar Health Research Institute, Hyattsville MD and Georgetown-Howard Universities Center for Clinical and Translational Science, Washington, DC, USADepartment of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, NC, USAUniversity 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, USACardiovascular 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, USACenter for American Indian Health Research, Department of Biostatistics and Epidemiology, Hudson College of Public Health, The University of Oklahoma Health Sciences Center, Oklahoma, OK, USAThe Institute for Translational Genomics and Population Sciences, Department of Pediatrics, The Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center, Torrance, CA USADepartment of Neurology, Epidemiology and Public Health, Miller School of Medicine, University of Miami, Miami, FL, USAThe Institute for Translational Genomics and Population Sciences, Department of Pediatrics, The Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center, Torrance, CA USAUnidad de Investigación Médica en Bioquímica, Hospital de Especialidades, Centro Médico Nacional Siglo XXI, Instituto Mexicano del Seguro Social, Mexico City, MexicoBrown Foundation Institute of Molecular Medicine, Houston, TX, USAInstituto René Rachou, Fundação Oswaldo Cruz, Belo Horizonte, BrazilLaboratório 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, USAPopulation Health Research Institute, Hamilton, ON, Canada; Department of Pathology and Molecular Medicine, McMaster University, Hamilton, ON, CanadaCardiovascular 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, USATexas Biomedical Research Institute, San Antonio, TX, USADepartment of Medicine, University of Mississippi Medical Center, Jackson, MS, USADepartment of Biomedical Informatics, University of Colorado Anschutz Medical Campus, Aurora, CO, USADepartment of Biostatistics, University of North Carolina at Chapel Hill, Chapel Hill, NC, USANational Institute on Minority Health and Health Disparities, National Institutes of Health, Bethesda, MD, USAThe Charles Bronfman Institute of Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USASchool 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, AustraliaDivision 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, UKDepartment of Public Health Sciences, School of Medicine, University of California Davis, Davis, CA, USACenter for Research on Genomics and Global Health, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USACentre for Genetics and Genomics Versus Arthritis, Centre for Musculoskeletal Research, The University of Manchester, Manchester, UK; Corresponding authorDepartment of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA; Corresponding authorSummary: 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.http://www.sciencedirect.com/science/article/pii/S2666979X23003129kidney functionchronic kidney diseasegenome-wide association studymulti-ancestryadmixed populationseGFR |
| spellingShingle | 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 Genome-wide study investigating effector genes and polygenic prediction for kidney function in persons with ancestry from Africa and the Americas Cell Genomics kidney function chronic kidney disease genome-wide association study multi-ancestry admixed populations eGFR |
| title | Genome-wide study investigating effector genes and polygenic prediction for kidney function in persons with ancestry from Africa and the Americas |
| title_full | Genome-wide study investigating effector genes and polygenic prediction for kidney function in persons with ancestry from Africa and the Americas |
| title_fullStr | Genome-wide study investigating effector genes and polygenic prediction for kidney function in persons with ancestry from Africa and the Americas |
| title_full_unstemmed | Genome-wide study investigating effector genes and polygenic prediction for kidney function in persons with ancestry from Africa and the Americas |
| title_short | Genome-wide study investigating effector genes and polygenic prediction for kidney function in persons with ancestry from Africa and the Americas |
| title_sort | genome wide study investigating effector genes and polygenic prediction for kidney function in persons with ancestry from africa and the americas |
| topic | kidney function chronic kidney disease genome-wide association study multi-ancestry admixed populations eGFR |
| url | http://www.sciencedirect.com/science/article/pii/S2666979X23003129 |
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