Whole genome sequence analyses of eGFR in 23,732 people representing multiple ancestries in the NHLBI trans-omics for precision medicine (TOPMed) consortium.

Alleles Gene Frequency Genetic Predisposition to Disease Genome-Wide Association Study Genomics / methods Glomerular Filtration Rate Humans Male National Heart, Lung, and Blood Institute (U.S.) Polymorphism, Single Nucleotide Precision Medicine / methods Public Health Surveillance Quantitative Trait, Heritable United States / epidemiology Whole Genome Sequencing
Ancestry-specific variants Kidney traits Rare variants Whole genome sequencing

Journal

EBioMedicine
ISSN: 2352-3964
Titre abrégé: EBioMedicine
Pays: Netherlands
ID NLM: 101647039

Informations de publication

Date de publication:
Jan 2021
Historique:
received: 06 07 2020
revised: 10 11 2020
accepted: 18 11 2020
pubmed: 9 1 2021
medline: 6 10 2021
entrez: 8 1 2021
Statut: ppublish

Résumé

Genetic factors that influence kidney traits have been understudied for low frequency and ancestry-specific variants. We combined whole genome sequencing (WGS) data from 23,732 participants from 10 NHLBI Trans-Omics for Precision Medicine (TOPMed) Program multi-ethnic studies to identify novel loci for estimated glomerular filtration rate (eGFR). Participants included European, African, East Asian, and Hispanic ancestries. We applied linear mixed models using a genetic relationship matrix estimated from the WGS data and adjusted for age, sex, study, and ethnicity. When testing single variants, we identified three novel loci driven by low frequency variants more commonly observed in non-European ancestry (PRKAA2, rs180996919, minor allele frequency [MAF] 0.04%, P = 6.1 × 10 This study highlights challenges in studying variants influencing kidney traits that are low frequency in populations and more common in non-European ancestry.

Sections du résumé

BACKGROUND BACKGROUND
Genetic factors that influence kidney traits have been understudied for low frequency and ancestry-specific variants.
METHODS METHODS
We combined whole genome sequencing (WGS) data from 23,732 participants from 10 NHLBI Trans-Omics for Precision Medicine (TOPMed) Program multi-ethnic studies to identify novel loci for estimated glomerular filtration rate (eGFR). Participants included European, African, East Asian, and Hispanic ancestries. We applied linear mixed models using a genetic relationship matrix estimated from the WGS data and adjusted for age, sex, study, and ethnicity.
FINDINGS RESULTS
When testing single variants, we identified three novel loci driven by low frequency variants more commonly observed in non-European ancestry (PRKAA2, rs180996919, minor allele frequency [MAF] 0.04%, P = 6.1 × 10
INTERPRETATION CONCLUSIONS
This study highlights challenges in studying variants influencing kidney traits that are low frequency in populations and more common in non-European ancestry.

Identifiants

DOI: 10.1016/j.ebiom.2020.103157 PMID: 33418499 PMC: PMC7804602
pubmed: 33418499
pii: S2352-3964(20)30533-8
doi: 10.1016/j.ebiom.2020.103157
pmc: PMC7804602
pii:
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

103157

Subventions

Organisme : NHLBI NIH HHS
ID : R01 HL120393
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK117445
Pays : United States
Organisme : NHGRI NIH HHS
ID : R01 HG010869
Pays : United States
Organisme : NHLBI NIH HHS
ID : R21 HL123677
Pays : United States
Organisme : NIMHD NIH HHS
ID : R01 MD012765
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL117626
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL149683
Pays : United States
Organisme : NIA NIH HHS
ID : K01 AG059898
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL131136
Pays : United States
Organisme : NHGRI NIH HHS
ID : R01 HG009974
Pays : United States
Organisme : NHLBI NIH HHS
ID : R21 HL140385
Pays : United States
Organisme : NIDDK NIH HHS
ID : P30 DK072488
Pays : United States
Organisme : NHLBI NIH HHS
ID : HHSN268201800001C
Pays : United States

Informations de copyright

Copyright © 2020 The Author(s). Published by Elsevier B.V. All rights reserved.

Déclaration de conflit d'intérêts

Declaration of Competing Interest GRA is employed by Regeneron Pharmaceuticals and he owns stock and stock options for Regeneron Pharmaceuticals. BMP serves on the Steering Committee of the Yale Open Data Access Project funded by Johnson & Johnson. BMP reports serving on the Steering Committee of the Yale Open Data Access Project funded by Johnson & Johnson. Y-DIC, LRY, JCM, BDM, JIR, KDT, JPL, EB, JAS, GRA report grants from NIH during the conduct of the study. Remaining authors have nothing to disclose.

Auteurs

Bridget M Lin (BM)

Department of Biostatistics, University of North Carolina, Chapel Hill, NC, United States.

Kelsey E Grinde (KE)

Department of Mathematics, Statistics, and Computer Science, Macalester College, St. Paul, MN, United States.

Jennifer A Brody (JA)

Cardiovascular Health Research Unit, Department of Medicine, University of Washington, Seattle, WA, United States.

Charles E Breeze (CE)

Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Department Health and Human Services, Bethesda, MD, United States; UCL Cancer Institute, University College London, London WC1E 6BT, United Kingdom; Altius Institute for Biomedical Sciences, Seattle, WA 98121, United States.

Laura M Raffield (LM)

Department of Genetics, University of North Carolina, Chapel Hill, NC, United States.

Josyf C Mychaleckyj (JC)

Center for Public Health Genomics, University of Virginia, Charlottesville, VA, United States.

Timothy A Thornton (TA)

Department of Biostatistics, University of Washington, Seattle, WA, United States.

James A Perry (JA)

Division of Endocrinology, Diabetes and Nutrition, and Program for Personalized and Genomic Medicine, University of Maryland School of Medicine, Baltimore, MD, United States.

Leslie J Baier (LJ)

Phoenix Epidemiology and Clinical Research Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Phoenix, AZ, United States.

Lisa de Las Fuentes (L)

Cardiovascular Division, Washington University School of Medicine, St. Louis, MO, United States.

Xiuqing Guo (X)

The Institute for Translational Genomics and Population Sciences, Department of Pediatrics, The Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center, Torrance, CA United States.

Benjamin D Heavner (BD)

Department of Biostatistics, University of Washington, Seattle, WA, United States.

Robert L Hanson (RL)

Phoenix Epidemiology and Clinical Research Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Phoenix, AZ, United States.

Yi-Jen Hung (YJ)

Endocrinology and Metabolism, Tri-Service General Hospital Songshan branch, Taipei, Taiwan.

Huijun Qian (H)

Department of Statistics and Operations Research, University of North Carolina, Chapel Hill, NC, United States.

Chao A Hsiung (CA)

Endocrinology and Metabolism, National Taiwan University Hospital, Taipei, Taiwan.

Shih-Jen Hwang (SJ)

National Heart, Lung, and Blood Institute Framingham Heart Study, Framingham, MA, United States; National Heart, Lung and Blood Institute, Population Sciences Branch, Division of Intramural Research, Bethesda, MD, United States.

Margaret R Irvin (MR)

Department of Epidemiology, University of Alabama at Birmingham, Birmingham, AL, United States.

Deepti Jain (D)

Department of Biostatistics, University of Washington, Seattle, WA, United States.

Tanika N Kelly (TN)

Department of Epidemiology, Tulane University School of Public Health and Tropical Medicine, New Orleans, LA, United States.

Sayuko Kobes (S)

Phoenix Epidemiology and Clinical Research Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Phoenix, AZ, United States.

Leslie Lange (L)

Division of Biomedical Informatics and Personalized Medicine, Department of Medicine, University of Colorado Anschutz Medical Campus, Denver, CO, United States.

James P Lash (JP)

Department of Medicine, University of Illinois, Chicago, IL, United States.

Yun Li (Y)

Department of Biostatistics, University of North Carolina, Chapel Hill, NC, United States; Department of Genetics, University of North Carolina, Chapel Hill, NC, United States.

Xiaoming Liu (X)

USF Genomics & College of Public Health, University of South Florida, Tampa, FL, United States.

Xuenan Mi (X)

Department of Epidemiology, Tulane University School of Public Health and Tropical Medicine, New Orleans, LA, United States.

Solomon K Musani (SK)

Department of Medicine, University of Mississippi Medical Center, Jackson, MS, United States.

George J Papanicolaou (GJ)

Epidemiology Branch, National Heart, Lung, and Blood Institute, Bethesda, MA, United States.

Afshin Parsa (A)

Division of Kidney, Urologic and Hematologic Diseases, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MA, United States.

Alex P Reiner (AP)

Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA, United States.

Shabnam Salimi (S)

Epidemiology and Public Health, University of Maryland School of Medicine, Baltimore, MD, United States.

Wayne H-H Sheu (WH)

Endocrinology & Metabolism, Taichung Veterans General Hospital, Taichung, Taiwan.

Alan R Shuldiner (AR)

Division of Endocrinology, Diabetes and Nutrition, and Program for Personalized and Genomic Medicine, University of Maryland School of Medicine, Baltimore, MD, United States.

Kent D Taylor (KD)

The Institute for Translational Genomics and Population Sciences, Department of Pediatrics, The Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center, Torrance, CA United States.

Albert V Smith (AV)

Department of Biostatistics, University of Michigan, Ann Arbor, MI, United States.

Jennifer A Smith (JA)

Department of Epidemiology, University of Michigan, Ann Arbor, MI, United States.

Adrienne Tin (A)

Department of Medicine, University of Mississippi Medical Center, Jackson, MS, United States; Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, United States.

Dhananjay Vaidya (D)

Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, United States.

Robert B Wallace (RB)

University of Iowa College of Public Health, Iowa City, IA, United States.

Kenichi Yamamoto (K)

Department of Statistical Genetics, Osaka University Graduate School of Medicine, Suita 565-0871, Japan; Department of Pediatrics, Osaka University Graduate School of Medicine, Suita 565-0871, Japan.

Saori Sakaue (S)

Department of Statistical Genetics, Osaka University Graduate School of Medicine, Suita 565-0871, Japan; Department of Allergy and Rheumatology, Graduate School of Medicine, the University of Tokyo, Tokyo 113-8655, Japan.

Koichi Matsuda (K)

Department of Computational Biology and Medical Sciences, Graduate school of Frontier Sciences, The University of Tokyo, Tokyo 108-8639, Japan.

Yoichiro Kamatani (Y)

Laboratory for Statistical Analysis, RIKEN Center for Integrative Medical Sciences, Yokohama 230-0045, Japan; Laboratory of Complex Trait Genomics, Department of Computational Biology and Medical Sciences, Graduate School of Frontier Sciences, the University of Tokyo, Tokyo 108-8639, Japan.

Yukihide Momozawa (Y)

Laboratory for Genotyping Development, RIKEN Center for Integrative Medical Sciences, Yokohama 230-0045, Japan.

Lisa R Yanek (LR)

Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, United States.

Betsi A Young (BA)

Kidney Research Institute and Division of Nephrology, University of Washington, Seattle, WA, United States.

Wei Zhao (W)

Department of Epidemiology, University of Michigan, Ann Arbor, MI, United States.

Yukinori Okada (Y)

Department of Statistical Genetics, Osaka University Graduate School of Medicine, Suita 565-0871, Japan; Laboratory for Statistical Analysis, RIKEN Center for Integrative Medical Sciences, Yokohama 230-0045, Japan; Integrated Frontier Research for Medical Science Division, Institute for Open and Transdisciplinary Research Initiatives, Osaka University, Suita 565-0871, Japan; Laboratory of Statistical Immunology, World Premier International Immunology Frontier Research Center (WPI-IFReC), Osaka University, Suita 565-0871, Japan.

Gonzalo Abecasis (G)

Department of Biostatistics and Center for Statistical Genetics, University of Michigan, An Arbor, MI, United States; Regeneron Pharmaceuticals, Tarrytown, NY, United States.

Bruce M Psaty (BM)

Cardiovascular Health Research Unit, Department of Medicine, University of Washington, Seattle, WA, United States; Departments of Epidemiology and Health Services, University of Washington, Seattle, WA, United States.

Donna K Arnett (DK)

College of Public Health, Dean's Office, University of Kentucky, Lexington, KY, United States.

Eric Boerwinkle (E)

Human Genetics Center, Department of Epidemiology, Human Genetics, and Environmental Sciences, School of Public Health, The University of Texas Health Science Center at Houston, Houston, TX, United States; Human Genome Sequencing Center, Baylor College of Medicine, Houston, TX, United States.

Jianwen Cai (J)

Department of Biostatistics, University of North Carolina, Chapel Hill, NC, United States.

Ida Yii-Der Chen (I)

The Institute for Translational Genomics and Population Sciences, Department of Pediatrics, The Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center, Torrance, CA United States.

Adolfo Correa (A)

Department of Medicine, University of Mississippi Medical Center, Jackson, MS, United States.

L Adrienne Cupples (LA)

National Heart, Lung, and Blood Institute Framingham Heart Study, Framingham, MA, United States; Department of Biostatistics, Boston University, Boston, MA, United States.

Jiang He (J)

Department of Epidemiology, Tulane University School of Public Health and Tropical Medicine, New Orleans, LA, United States.

Sharon Lr Kardia (SL)

Department of Epidemiology, University of Michigan, Ann Arbor, MI, United States.

Charles Kooperberg (C)

Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA, United States.

Rasika A Mathias (RA)

Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, United States.

Braxton D Mitchell (BD)

Division of Endocrinology, Diabetes and Nutrition, and Program for Personalized and Genomic Medicine, University of Maryland School of Medicine, Baltimore, MD, United States; Geriatrics Research and Education Clinical Center, Baltimore Veterans Administration Medical Center, Baltimore, MD, United States.

Deborah A Nickerson (DA)

Department of Genome Sciences, University of Washington, Seattle, WA, United States.

Steve T Turner (ST)

Department of Internal Medicine, Mayo Clinic, Rochester, MN, United States.

Ramachandran S Vasan (RS)

Division of Preventive Medicine and Epidemiology and Cardiology, Boston University School of Medicine, Boston, MA, United States.

Jerome I Rotter (JI)

The Institute for Translational Genomics and Population Sciences, Department of Pediatrics, The Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center, Torrance, CA United States.

Daniel Levy (D)

National Heart, Lung, and Blood Institute Framingham Heart Study, Framingham, MA, United States; National Heart, Lung and Blood Institute, Population Sciences Branch, Division of Intramural Research, Bethesda, MD, United States.

Holly J Kramer (HJ)

Department of Public Health Sciences and Medicine, Loyola University Chicago, Maywood, IL, United States; Division of Nephrology and Hypertension, Loyola University Chicago, Maywood, IL, United States.

Anna Köttgen (A)

Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, United States; Institute of Genetic Epidemiology, Faculty of Medicine and Medical Center, University of Freiburg, Freiburg, Germany.
Members listed at the end of the article.
Members listed at the end of the article.

Stephen S Rich (SS)

Center for Public Health Genomics, University of Virginia, Charlottesville, VA, United States.

Dan-Yu Lin (DY)

Department of Biostatistics, University of North Carolina, Chapel Hill, NC, United States.

Sharon R Browning (SR)

Department of Biostatistics, University of Washington, Seattle, WA, United States.

Nora Franceschini (N)

Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, NC, United States. Electronic address: noraf@unc.edu.

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Classifications MeSH

questionsmedicales.fr › Phénomènes génétiques › Structures génétiques › Génome › Composants de génome › Gènes › Allèles › Whole genome sequence analyses of eGFR in...
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