Whole-genome sequencing uncovers two loci for coronary artery calcification and identifies ARSE as a regulator of vascular calcification.

Journal

Nature cardiovascular research
ISSN: 2731-0590
Titre abrégé: Nat Cardiovasc Res
Pays: England
ID NLM: 9918284280206676

Informations de publication

Date de publication:
Dec 2023
Historique:
medline: 31 5 2024
pubmed: 31 5 2024
entrez: 31 5 2024
Statut: ppublish

Résumé

Coronary artery calcification (CAC) is a measure of atherosclerosis and a well-established predictor of coronary artery disease (CAD) events. Here we describe a genome-wide association study (GWAS) of CAC in 22,400 participants from multiple ancestral groups. We confirmed associations with four known loci and identified two additional loci associated with CAC (

Identifiants

DOI: 10.1038/s44161-023-00375-y PMID: 38817323 PMC: PMC11138106
pubmed: 38817323
doi: 10.1038/s44161-023-00375-y
pmc: PMC11138106
doi:

Types de publication

Journal Article

Langues

eng

Pagination

1159-1172

Déclaration de conflit d'intérêts

Bruce M. Psaty serves on the Steering Committee of the Yale Open Data Access Project funded by Johnson & Johnson. Leslie S. Emery is now an employee of Celgene/Bristol Myers Squibb. Celgene/Bristol Myers Squibb had no role in the funding, design, conduct, or interpretation of this study. Nathan O. Stitziel has received research funding from Regeneron Pharmaceuticals, unrelated to this work. Karine A. Viaud-Martinez is an employee at Illumina Inc. Ryan W. Kim is an employee at Psomagen Inc. Roxona Mehran reports institutional research grants from Abbott Laboratories, Abiomed, Applied Therapeutics, AstraZeneca, Bayer, Beth Israel Deaconess, Bristol-Myers Squibb, CERC, Chiesi, Concept Medical, CSL Behring, DSI, Medtronic, Novartis Pharmaceuticals, OrbusNeich; consultant fees from Abbott Laboratories, Boston Scientific, CardiaWave, Chiesi, Janssen Scientific Affairs, Medscape/WebMD, Medtelligence (Janssen Scientific Affairs), Roivant Sciences, Sanofi, Siemens Medical Solutions; consultant fees paid to the institution from Abbott Laboratories, Bristol-Myers Squibb; advisory board, funding paid to the institution from Spectranetics/Philips/Volcano Corp; consultant (spouse) from Abiomed, The Medicines Company, Merck; Equity <1% from Claret Medical, Elixir Medical; DSMB Membership fees paid to the institution from Watermark Research Partners; consulting (no fee) from Idorsia Pharmaceuticals Ltd., Regeneron Pharmaceuticals; Associate Editor for ACC, AMA. Rajeev Malhotra is a consultant for MyoKardia (now owned by BMS), Epizon Pharma, Renovacor, and Third Pole, a co-founder of Patch and Angea Biotherapeutics, and has received research funding from Angea Biotherapeutics, Bayer Pharmaceuticals, and Amgen. Adrienne M. Stilp receives funding from Seven Bridges Genomics to develop tools for the NHLBI BioData Catalyst consortium. Pradeep Natarajan reports grants from Amgen, Apple, Boston Scientific, AstraZeneca, Allelica, Novartis, and Genentech, consulting income from GV, Blackstone Life Sciences, Foresite Labs, Apple, AstraZeneca, Allelica, Novartis, HeartFlow, and Genentech, is a scientific advisor to Esperion Therapeutics, Preciseli, and TenSixteen Bio, is a scientific co-founder of TenSixteen Bio, and spousal employment at Vertex, all unrelated to the present work. Clint L. Miller received a research grant from AstraZeneca for an unrelated project. The remaining authors declare no competing interests.

Auteurs

Paul S de Vries (PS)

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, USA.

Matthew P Conomos (MP)

Genetic Analysis Center, Department of Biostatistics, School of Public Health, University of Washington, Seattle, WA, USA.

Kuldeep Singh (K)

Cardiovascular Research Center, Division of Cardiology, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.

Christopher J Nicholson (CJ)

Cardiovascular Research Center, Division of Cardiology, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.

Deepti Jain (D)

Genetic Analysis Center, Department of Biostatistics, School of Public Health, University of Washington, Seattle, WA, USA.

Natalie R Hasbani (NR)

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, USA.

Wanlin Jiang (W)

Cardiovascular Research Center, Division of Cardiology, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.

Sujin Lee (S)

Cardiovascular Research Center, Division of Cardiology, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.

Christian L Lino Cardenas (CLL)

Cardiovascular Research Center, Division of Cardiology, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.

Sharon M Lutz (SM)

PRecisiOn Medicine Translational Research (PROMoTeR) Center, Department of Population Medicine, Harvard Medical School and Harvard Pilgrim Health Care Institute, Boston, MA, USA.
Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, MA, USA.

Doris Wong (D)

Center for Public Health Genomics, University of Virginia School of Medicine, Charlottesville, VA, USA.

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, USA.

Jie Yao (J)

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.

Erica P Young (EP)

Cardiovascular Division, Department of Internal Medicine, Washington University School of Medicine, St. Louis, MO, USA.

Catherine Tcheandjieu (C)

VA Palo Alto Healthcare System, Palo Alto, CA, USA.
Department of Medicine, Stanford University School of Medicine, Stanford, CA, USA.

Austin T Hilliard (AT)

VA Palo Alto Healthcare System, Palo Alto, CA, USA.
Palo Alto Veterans Institute for Research, Palo Alto, CA, USA.

Joshua C Bis (JC)

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

Lawrence F Bielak (LF)

School of Public Health, Department of Epidemiology, University of Michigan, Ann Arbor, MI, USA.

Michael R Brown (MR)

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, USA.

Shaila Musharoff (S)

VA Palo Alto Healthcare System, Palo Alto, CA, USA.
Department of Genetics, Stanford University School of Medicine, Stanford, CA, USA.

Shoa L Clarke (SL)

VA Palo Alto Healthcare System, Palo Alto, CA, USA.
Department of Medicine, Stanford University School of Medicine, Stanford, CA, USA.

James G Terry (JG)

Department of Radiology, Vanderbilt Translational and Clinical Cardiovascular Research Center, Vanderbilt University Medical Center, Nashville, TN, USA.

Nicholette D Palmer (ND)

Department of Biochemistry, Wake Forest School of Medicine, Winston-Salem, NC, USA.

Lisa R Yanek (LR)

Division of General Internal Medicine, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA.

Huichun Xu (H)

Division of Endocrinology, Diabetes and Nutrition, Department of Medicine, University of Maryland School of Medicine, Baltimore, MD, USA.

Nancy Heard-Costa (N)

Boston University School of Medicine, Boston, MA, USA.
Boston University and National Heart, Lung, and Blood Institute's Framingham Heart Study, Framingham, MA, USA.

Jennifer Wessel (J)

Department of Epidemiology, Fairbanks School of Public Health, Indiana University, Indianapolis, IN, USA.
Diabetes Translational Research Center, Indiana University, Indianapolis, IN, USA.

Margaret Sunitha Selvaraj (MS)

Cardiovascular Research Center and Center for Genomic Medicine, Massachusetts General Hospital, Boston, MA, USA.
Program in Medical and Population Genetics, Broad Institute of Harvard and MIT, Cambridge, MA, USA.
Department of Medicine, Harvard Medical School, Boston, MA, USA.

Rebecca H Li (RH)

Cardiovascular Research Center, Division of Cardiology, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.

Xiao Sun (X)

School of Public Health and Tropical Medicine, Department of Epidemiology, Tulane University, New Orleans, LA, USA.
College of Medicine, Department of Medicine, Division of Nephrology, University of Illinois Chicago, Chicago, IL, USA.

Adam W Turner (AW)

Center for Public Health Genomics, University of Virginia School of Medicine, Charlottesville, VA, USA.

Adrienne M Stilp (AM)

Genetic Analysis Center, Department of Biostatistics, School of Public Health, University of Washington, Seattle, WA, USA.

Alyna Khan (A)

Genetic Analysis Center, Department of Biostatistics, School of Public Health, University of Washington, Seattle, WA, USA.

Anne B Newman (AB)

Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA, USA.

Asif Rasheed (A)

Center For Non-Communicable Diseases, Karachi, Pakistan.

Barry I Freedman (BI)

Section on Nephrology, Department of Internal Medicine, Wake Forest School of Medicine, Winston-Salem, NC, USA.

Brian G Kral (BG)

Division of Cardiology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA.

Caitlin P McHugh (CP)

Genetic Analysis Center, Department of Biostatistics, School of Public Health, University of Washington, Seattle, WA, USA.

Chani Hodonsky (C)

Center for Public Health Genomics, University of Virginia School of Medicine, Charlottesville, VA, USA.

Danish Saleheen (D)

Center For Non-Communicable Diseases, Karachi, Pakistan.
Department of Medicine, Columbia University Irving Medical Center, New York, NY, USA.
Department of Cardiology, Columbia University Irving Medical Center, New York, NY, USA.

David M Herrington (DM)

Department of Internal Medicine, Section of Cardiovascular Medicine, Wake Forest School of Medicine, Winston-Salem, NC, USA.

David R Jacobs (DR)

Division of Epidemiology and Community Health, University of Minnesota School of Public Health, Minneapolis, MN, USA.

Deborah A Nickerson (DA)

Department of Genome Sciences, University of Washington, Seattle, WA, USA.
Northwest Genomics Center, University of Washington, Seattle, WA, USA.

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, USA.
Human Genome Sequencing Center, Baylor College of Medicine, Houston, TX, USA.

Fei Fei Wang (FF)

Genetic Analysis Center, Department of Biostatistics, School of Public Health, University of Washington, Seattle, WA, USA.

Gerardo Heiss (G)

Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, NC, USA.

Goo Jun (G)

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, USA.

Greg L Kinney (GL)

Department of Epidemiology, Colorado School of Public Health, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.

Haakon H Sigurslid (HH)

Cardiovascular Research Center, Division of Cardiology, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.

HarshaVardhan Doddapaneni (H)

Human Genome Sequencing Center, Baylor College of Medicine, Houston, TX, USA.

Ira M Hall (IM)

Yale Center for Genomic Health, Yale School of Medicine, New Haven, CT, USA.

Isabela M Bensenor (IM)

Center for Clinical and Epidemiological Research, University Hospital, University of Sao Paulo Medical School, São Paulo, Brazil.

Jai Broome (J)

Genetic Analysis Center, Department of Biostatistics, School of Public Health, University of Washington, Seattle, WA, USA.

James D Crapo (JD)

Department of Medicine, National Jewish Health, Denver, CO, USA.

James G Wilson (JG)

Division of Cardiology, Beth Israel Deaconess Medical Center, Boston, MA, USA.

Jennifer A Smith (JA)

School of Public Health, Department of Epidemiology, University of Michigan, Ann Arbor, MI, USA.
Survey Research Center, Institute for Social Research, University of Michigan, Ann Arbor, MI, USA.

John Blangero (J)

Department of Human Genetics, University of Texas Rio Grande Valley School of Medicine, Brownsville, TX, USA.
South Texas Diabetes and Obesity Institute, University of Texas Rio Grande Valley School of Medicine, Brownsville, TX, USA.

Jose D Vargas (JD)

Medstar Heart and Vascular Institute, Medstar Georgetown University Hospital, Washington, DC, USA.

Jose Verdezoto Mosquera (JV)

Center for Public Health Genomics, University of Virginia School of Medicine, Charlottesville, VA, USA.

Joshua D Smith (JD)

Department of Genome Sciences, University of Washington, Seattle, WA, USA.
Northwest Genomics Center, University of Washington, Seattle, WA, USA.

Karine A Viaud-Martinez (KA)

Illumina Laboratory Services, Illumina Inc., San Diego, CA, USA.

Kathleen A Ryan (KA)

Division of Endocrinology, Diabetes and Nutrition, Department of Medicine, University of Maryland School of Medicine, Baltimore, MD, USA.

Kendra A Young (KA)

Department of Epidemiology, Colorado School of Public Health, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.

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, USA.

Leslie A Lange (LA)

Department of Medicine, University of Colorado Denver, Anschutz Medical Campus, Aurora, CO, USA.

Leslie S Emery (LS)

Genetic Analysis Center, Department of Biostatistics, School of Public Health, University of Washington, Seattle, WA, USA.

Marcio S Bittencourt (MS)

Center for Clinical and Epidemiological Research, University Hospital, University of Sao Paulo Medical School, São Paulo, Brazil.

Matthew J Budoff (MJ)

Department of Medicine, The Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center, Torrance, CA, USA.

May E Montasser (ME)

Division of Endocrinology, Diabetes and Nutrition, Department of Medicine, University of Maryland School of Medicine, Baltimore, MD, USA.

Miao Yu (M)

School of Public Health, Department of Epidemiology, University of Michigan, Ann Arbor, MI, USA.

Michael C Mahaney (MC)

Department of Human Genetics, University of Texas Rio Grande Valley School of Medicine, Brownsville, TX, USA.
South Texas Diabetes and Obesity Institute, University of Texas Rio Grande Valley School of Medicine, Brownsville, TX, USA.

Mohammed S Mahamdeh (MS)

Cardiovascular Research Center, Division of Cardiology, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.

Myriam Fornage (M)

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, USA.
Institute of Molecular Medicine, McGovern Medical School, The University of Texas Health Science Center at Houston, Houston, TX, USA.

Nora Franceschini (N)

Department of Epidemiology, Gillings School of Global Public health, University of North Carolina, Chapel Hill, NC, USA.

Paulo A Lotufo (PA)

Center for Clinical and Epidemiological Research, University Hospital, University of Sao Paulo Medical School, São Paulo, Brazil.

Pradeep Natarajan (P)

Cardiovascular Research Center and Center for Genomic Medicine, Massachusetts General Hospital, Boston, MA, USA.
Program in Medical and Population Genetics, Broad Institute of Harvard and MIT, Cambridge, MA, USA.
Department of Medicine, Harvard Medical School, Boston, MA, USA.

Quenna Wong (Q)

Genetic Analysis Center, Department of Biostatistics, School of Public Health, University of Washington, Seattle, WA, USA.

Rasika A Mathias (RA)

Division of General Internal Medicine, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Division of Allergy and Clinical Immunology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA.

Richard A Gibbs (RA)

Human Genome Sequencing Center, Baylor College of Medicine, Houston, TX, USA.
Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA.

Ron Do (R)

The Charles Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA.

Roxana Mehran (R)

Icahn School of Medicine at Mount Sinai, New York, NY, USA.

Russell P Tracy (RP)

Department of Pathology and Laboratory Medicine, Robert Larner, M.D. College of Medicine, University of Vermont, Burlington, VT, USA.

Ryan W Kim (RW)

Psomagen Inc., Rockville, MD, USA.

Sarah C Nelson (SC)

Genetic Analysis Center, Department of Biostatistics, School of Public Health, University of Washington, Seattle, WA, USA.

Scott M Damrauer (SM)

Corporal Michael J. Crescenz VA Medical Center, Philadelphia, PA, USA.
Department of Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.

Sharon L R Kardia (SLR)

School of Public Health, Department of Epidemiology, University of Michigan, Ann Arbor, MI, USA.

Stephen S Rich (SS)

Center for Public Health Genomics, University of Virginia School of Medicine, Charlottesville, VA, USA.

Valentin Fuster (V)

Centro Nacional de Investigaciones Cardiovasculares Carlos III, Madrid, Spain.
Mount Sinai Heart Center, New York, NY, USA.

Valerio Napolioni (V)

Genomic And Molecular Epidemiology (GAME) Lab, School of Biosciences and Veterinary Medicine, University of Camerino, Camerino, Italy.

Wei Zhao (W)

School of Public Health, Department of Epidemiology, University of Michigan, Ann Arbor, MI, USA.

Wenjie Tian (W)

Cardiovascular Research Center, Division of Cardiology, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.

Xianyong Yin (X)

Department of Biostatistics and Center for Statistical Genetics, University of Michigan, Ann Arbor, MI, USA.

Yuan-I Min (YI)

Jackson Heart Study, Department of Medicine, University of Mississippi Medical Center, Jackson, MS, USA.

Alisa K Manning (AK)

Clinical and Translation Epidemiology Unit, Department of Medicine, Massachusetts General Hospital, Boston, MA, USA.
Programs in Metabolism and Medical and Population Genetics, Broad Institute, Cambridge, MA, USA.

Gina Peloso (G)

Department of Biostatistics, Boston University School of Public Health, Boston, MA, USA.

Tanika N Kelly (TN)

College of Medicine, Department of Medicine, Division of Nephrology, University of Illinois Chicago, Chicago, IL, USA.

Christopher J O'Donnell (CJ)

VA Boston Healthcare System, Boston, MA, USA.
Department of Medicine, Brigham and Women's Hospital, Boston, MA, USA.

Alanna C Morrison (AC)

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, USA.

Joanne E Curran (JE)

Department of Human Genetics, University of Texas Rio Grande Valley School of Medicine, Brownsville, TX, USA.
South Texas Diabetes and Obesity Institute, University of Texas Rio Grande Valley School of Medicine, Brownsville, TX, USA.

Warren M Zapol (WM)

Department of Anesthesia, Critical Care and Pain Medicine at Massachusetts General Hospital, Boston, MA, USA.

Donald W Bowden (DW)

Department of Biochemistry, Wake Forest School of Medicine, Winston-Salem, NC, USA.

Lewis C Becker (LC)

Division of Cardiology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA.

Adolfo Correa (A)

Jackson Heart Study, Department of Medicine, University of Mississippi Medical Center, Jackson, MS, USA.
Department of Population Health Science, University of Mississippi Medical Center, Jackson, MS, USA.

Braxton D Mitchell (BD)

Division of Endocrinology, Diabetes and Nutrition, Department of Medicine, University of Maryland School of Medicine, Baltimore, MD, USA.
Geriatrics Research and Education Clinical Center, Baltimore Veterans Administration Medical Center, Baltimore, MD, USA.

Bruce M Psaty (BM)

Cardiovascular Health Research Unit, Department of Medicine, University of Washington, Seattle, WA, USA.
Department of Epidemiology, University of Washington, Seattle, WA, USA.
Department of Health Services, University of Washington, Seattle, WA, USA.

John Jeffrey Carr (JJ)

Department of Radiology, Vanderbilt Translational and Clinical Cardiovascular Research Center, Vanderbilt University Medical Center, Nashville, TN, USA.

Alexandre C Pereira (AC)

Department of Genetics, Harvard Medical School, Boston, MA, USA.
Laboratory of Genetics and Molecular Cardiology, Heart Institute, University of São Paulo, São Paulo, Brazil.

Themistocles L Assimes (TL)

VA Palo Alto Healthcare System, Palo Alto, CA, USA.
Department of Medicine, Stanford University School of Medicine, Stanford, CA, USA.

Nathan O Stitziel (NO)

Cardiovascular Division, Department of Internal Medicine, Washington University School of Medicine, St. Louis, MO, USA.
Department of Genetics, Washington University School of Medicine, St. Louis, MO, USA.
McDonnell Genome Institute, Washington University School of Medicine, St. Louis, MO, USA.

John E Hokanson (JE)

Department of Epidemiology, Colorado School of Public Health, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.

Cecelia A Laurie (CA)

Genetic Analysis Center, Department of Biostatistics, School of Public Health, University of Washington, Seattle, WA, USA.

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, USA.

Ramachandran S Vasan (RS)

Boston University and National Heart, Lung, and Blood Institute's Framingham Heart Study, Framingham, MA, USA.
Department of Medicine, Boston University School of Medicine, Boston, MA, USA.
Department of Epidemiology, Boston University School of Public Health, Boston, MA, USA.

Wendy S Post (WS)

Division of Cardiology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA.

Patricia A Peyser (PA)

School of Public Health, Department of Epidemiology, University of Michigan, Ann Arbor, MI, USA.

Clint L Miller (CL)

Center for Public Health Genomics, University of Virginia School of Medicine, Charlottesville, VA, USA.

Rajeev Malhotra (R)

Cardiovascular Research Center, Division of Cardiology, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.

Classifications MeSH