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

doi:10.1016/j.xgen.2023.100468

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Genome-wide study investigating effector genes and polygenic prediction for kidney function in persons with ancestry from Africa and the Americas

Journal article

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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, …

Cell genomics, p.100468

2023-12-20

DOI: https://doi.org/10.1016/j.xgen.2023.100468

PMID: 38190104

Appears in Miller School of Medicine - Latest Publications

Abstract

eGFR

chronic kidney disease

expression quantitative trait locus

kidney function

multi-ancestry

polygenic scores

admixed populations

genome-wide association study

fine-mapping

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 ), 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.

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Title: Genome-wide study investigating effector genes and polygenic prediction for kidney function in persons with ancestry from Africa and the Americas
Creators: Odessica Hughes - University of Manchester
Amy R Bentley - National Human Genome Research Institute
Charles E Breeze - National Institutes of Health
Francois Aguet - Broad Institute
Xiaoguang Xu - University of Manchester
Girish Nadkarni - Icahn School of Medicine at Mount Sinai
Quan Sun - University of North Carolina at Chapel Hill
Bridget M Lin - University of North Carolina at Chapel Hill
Thomas Gilliland - Broad Institute
Mariah C Meyer - University of Colorado Anschutz Medical Campus
Jiawen Du - University of North Carolina at Chapel Hill
Laura M Raffield - University of North Carolina at Chapel Hill
Holly Kramer - Loyola University Chicago
Robert W Morton - Population Health Research Institute
Mateus H Gouveia - National Human Genome Research Institute
Elizabeth G Atkinson - Baylor College of Medicine
Adan Valladares-Salgado - Centro Medico Nacional Siglo XXI
Niels Wacher-Rodarte - Centro Medico Nacional Siglo XXI
Nicole D Dueker - University of Miami
Xiuqing Guo - UCLA Medical Center
Yang Hai - Harbor–UCLA Medical Center
Adebowale Adeyemo - National Human Genome Research Institute
Lyle G Best - Missouri Breaks Industries Research
Jianwen Cai - University of North Carolina at Chapel Hill
Guanjie Chen - National Human Genome Research Institute
Michael Chong
Ayo Doumatey - National Human Genome Research Institute
James Eales - University of Manchester
Mark O Goodarzi - Cedars-Sinai Medical Center
Eli Ipp - Baylor College of Medicine
Marguerite Ryan Irvin - University of Alabama at Birmingham
Minzhi Jiang - University of North Carolina at Chapel Hill
Alana C Jones - University of Alabama at Birmingham
Charles Kooperberg - National Institutes of Health
Jose E Krieger - Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo
Ethan M Lange - University of Colorado Anschutz Medical Campus
Matthew B Lanktree - McMaster University
James P Lash - University of Illinois Urbana-Champaign
Paulo A Lotufo - Universidade de São Paulo
Ruth J F Loos
Vy Thi Ha My - Icahn School of Medicine at Mount Sinai
Jesús Peralta-Romero - Centro Medico Nacional Siglo XXI
Lihong Qi - Ronald Reagan UCLA Medical Center
Leslie J Raffel - University of California, Irvine
Stephen S Rich - University of Virginia
Erik J Rodriquez - National Heart Lung and Blood Institute
Eduardo Tarazona-Santos - Universidade Federal de Minas Gerais
Kent D Taylor - Harbor–UCLA Medical Center
Jason G Umans - Georgetown-Howard Universities Center for Clinical and Translational Science
Jia Wen - University of North Carolina at Chapel Hill
Bessie A Young
Zhi Yu
Ying Zhang - University of Oklahoma Health Sciences Center
Yii-Der Ida Chen - Harbor–UCLA Medical Center
Tanja Rundek - University of Miami
Jerome I Rotter - Harbor–UCLA Medical Center
Miguel Cruz - Centro Medico Nacional Siglo XXI
Myriam Fornage - Brown Foundation
Maria Fernanda Lima-Costa - Instituto René Rachou, Fundação Oswaldo Cruz, Belo Horizonte, Brazil
Alexandre C Pereira
Guillaume Paré
Pradeep Natarajan
Shelley A Cole - Dr. John T. Macdonald Foundation
April P Carson - University of Mississippi Medical Center
Leslie A Lange - University of Colorado Anschutz Medical Campus
Yun Li - Baylor College of Medicine
Eliseo J Perez-Stable - National Institute on Minority Health and Health Disparities
Ron Do - Centro Medico Nacional Siglo XXI
Fadi J Charchar
Maciej Tomaszewski
Josyf C Mychaleckyj - University of California, Davis
Charles Rotimi - National Institutes of Health
Andrew P Morris - University of Manchester
Nora Franceschini - University of North Carolina at Chapel Hill
Publication Details: Cell genomics, p.100468
Academic Unit: Miller School of Medicine; UMMG Department of Neurology; John P. Hussman Institute for Human Genomics
Language: English
Resource Type: Journal article
PMID: 38190104
Record Identifier: 991031982272902976