Multi-ancestry genome-wide study identifies effector genes and druggable pathways for coronary artery calcification

被引：0

作者：

Maryam Kavousi

Maxime M. Bos

Hanna J. Barnes

Christian L. Lino Cardenas

Doris Wong

Haojie Lu

Chani J. Hodonsky

Lennart P. L. Landsmeer

Adam W. Turner

Minjung Kho

Natalie R. Hasbani

Paul S. de Vries

Donald W. Bowden

Sandesh Chopade

Joris Deelen

Ernest Diez Benavente

Xiuqing Guo

Edith Hofer

Shih-Jen Hwang

Sharon M. Lutz

Leo-Pekka Lyytikäinen

Lotte Slenders

Albert V. Smith

Maggie A. Stanislawski

Jessica van Setten

Quenna Wong

Lisa R. Yanek

Diane M. Becker

Marian Beekman

Matthew J. Budoff

Mary F. Feitosa

Chris Finan

Austin T. Hilliard

Sharon L. R. Kardia

Jason C. Kovacic

Brian G. Kral

Carl D. Langefeld

Lenore J. Launer

Shaista Malik

Firdaus A. A. Mohamed Hoesein

Michal Mokry

Reinhold Schmidt

Jennifer A. Smith

Kent D. Taylor

James G. Terry

Jeroen van der Grond

Joyce van Meurs

Rozemarijn Vliegenthart

Jianzhao Xu

Kendra A. Young

机构：

[1] University Medical Center Rotterdam,Department of Epidemiology, Erasmus MC

[2] Massachusetts General Hospital,Cardiovascular Research Center, Cardiology Division, Department of Medicine

[3] Harvard Medical School,Department of Biochemistry and Molecular Genetics

[4] University of Virginia,Center for Public Health Genomics

[5] University of Virginia,Department of Internal Medicine, Erasmus MC

[6] University Medical Center Rotterdam,Central Diagnostics Laboratory, Division Laboratories, Pharmacy, and Biomedical Genetics, University Medical Center Utrecht

[7] Utrecht University,Department of Epidemiology, School of Public Health

[8] University of Michigan,Graduate School of Data Science

[9] Seoul National University,Human Genetics Center, Department of Epidemiology, Human Genetics, and Environmental Sciences, School of Public Health

[10] The University of Texas Health Center at Houston,Department of Biochemistry

[11] Wake Forest University Health Sciences,Institute of Cardiovascular Science, Faculty of Population Health

[12] University College London,Biomedical Data Sciences, Molecular Epidemiology

[13] University College London British Heart Foundation Research Accelerator Centre,Laboratory of Experimental Cardiology, Division of Heart and Lungs

[14] Leiden University Medical Center,The Institute for Translational Genomics and Population Sciences, Department of Pediatrics

[15] Max Planck Institute for Biology of Aging,Department of Neurology, Clinical Division of Neurogeriatrics

[16] University Medical Center Utrecht and Utrecht University,Institute for Medical Informatics, Statistics and Documentation

[17] The Lundquist Institute for Biomedical Innovation (formerly Los Angeles Biomedical Research Institute) at Harbor-UCLA Medical Center,Department of Clinical Chemistry, Fimlab Laboratories and Finnish Cardiovascular Research Center

[18] Medical University of Graz,Tampere, Faculty of Medicine and Health Technology

[19] Medical University of Graz,Department of Biostatistics

[20] Population Sciences,Department of Biomedical Informatics

[21] NHLBI/NIH,Department of Cardiology, Division of Heart and Lungs

[22] Population Medicine,Department of Biostatistics

[23] Harvard Medical School and Harvard Pilgrim Health Care,GeneSTAR Research Program, Department of Medicine

[24] Tampere University,Department of Genetics, Division of Statistical Genomics

[25] University of Michigan,St Vincent’s Clinical School

[26] Icelandic Heart Association,Department of Biostatistical Sciences and Data Science

[27] University of Colorado,Susan Samueli Integrative Health Institute, Department of Medicine

[28] Anschutz Medical Campus,Department of Radiology

[29] University Medical Center Utrecht and Utrecht University,Survey Research Center, Institute for Social Research

[30] University of Washington,Department of Radiology and Radiological Sciences

[31] Johns Hopkins University School of Medicine,Department of Radiology

[32] Washington University School of Medicine,Department of Radiology, University of Groningen

[33] VA Palo Alto Healthcare System,Department of Epidemiology

[34] Victor Chang Cardiac Research Institute,Department of Internal Medicine, Division of Cardiology

[35] University of NSW,Department of Medicine, Division of Cardiovascular Medicine

[36] The Zena and Michael A. Wiener Cardiovascular Institute,Department of Radiology and Nuclear Medicine, Erasmus MC

[37] Icahn School of Medicine at Mount Sinai,Department of Biostatistics, School of Public Health

[38] Wake Forest University Health Sciences,Department of Vascular Surgery

[39] Laboratory of Epidemiology and Population Sciences,Department of Medical Biochemistry, Experimental Vascular Biology, Amsterdam Cardiovascular Sciences: Atherosclerosis and Ischemic syndromes, Amsterdam Infection and Immunity: Inflammatory diseases, Amster

[40] National Institute on Aging,Institute of Molecular Medicine, McGovern Medical School

[41] National Institutes of Health,Department of Internal Medicine

[42] University of California Irvine,Faculty of Medicine, School of Public Health

[43] University Medical Center Utrecht and Utrecht University,Image Sciences Institute

[44] University of Michigan,Department of Biomedical Engineering and Physics, Amsterdam University Medical Center

[45] Vanderbilt University Medical Center,Division of Epidemiology and Community Health, School of Public Health

[46] Leiden University Medical Center,Department of Clinical Physiology, Tampere University Hospital and Finnish Cardiovascular Research Center

[47] University Medical Center Groningen,Tampere, Faculty of Medicine and Health Technology

[48] University of Colorado,Centre for Population Health Research

[49] Anschutz Medical Campus,Research Centre of Applied and Preventive Cardiovascular Medicine

[50] Medical University of Graz,Department of Clinical Physiology and Nuclear Medicine

来源：

Nature Genetics | 2023年 / 55卷

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学科分类号：

摘要：

Coronary artery calcification (CAC), a measure of subclinical atherosclerosis, predicts future symptomatic coronary artery disease (CAD). Identifying genetic risk factors for CAC may point to new therapeutic avenues for prevention. Currently, there are only four known risk loci for CAC identified from genome-wide association studies (GWAS) in the general population. Here we conducted the largest multi-ancestry GWAS meta-analysis of CAC to date, which comprised 26,909 individuals of European ancestry and 8,867 individuals of African ancestry. We identified 11 independent risk loci, of which eight were new for CAC and five had not been reported for CAD. These new CAC loci are related to bone mineralization, phosphate catabolism and hormone metabolic pathways. Several new loci harbor candidate causal genes supported by multiple lines of functional evidence and are regulators of smooth muscle cell-mediated calcification ex vivo and in vitro. Together, these findings help refine the genetic architecture of CAC and extend our understanding of the biological and potential druggable pathways underlying CAC.

引用

页码：1651 / 1664

页数：13

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