Nature Communications (Dec 2020)
Loss-of-function genomic variants highlight potential therapeutic targets for cardiovascular disease
- Jonas B. Nielsen,
- Oren Rom,
- Ida Surakka,
- Sarah E. Graham,
- Wei Zhou,
- Tanmoy Roychowdhury,
- Lars G. Fritsche,
- Sarah A. Gagliano Taliun,
- Carlo Sidore,
- Yuhao Liu,
- Maiken E. Gabrielsen,
- Anne Heidi Skogholt,
- Brooke Wolford,
- William Overton,
- Ying Zhao,
- Jin Chen,
- He Zhang,
- Whitney E. Hornsby,
- Akua Acheampong,
- Austen Grooms,
- Amanda Schaefer,
- Gregory J. M. Zajac,
- Luis Villacorta,
- Jifeng Zhang,
- Ben Brumpton,
- Mari Løset,
- Vivek Rai,
- Pia R. Lundegaard,
- Morten S. Olesen,
- Kent D. Taylor,
- Nicholette D. Palmer,
- Yii-Der Chen,
- Seung H. Choi,
- Steven A. Lubitz,
- Patrick T. Ellinor,
- Kathleen C. Barnes,
- Michelle Daya,
- Nicholas Rafaels,
- Scott T. Weiss,
- Jessica Lasky-Su,
- Russell P. Tracy,
- Ramachandran S. Vasan,
- L. Adrienne Cupples,
- Rasika A. Mathias,
- Lisa R. Yanek,
- Lewis C. Becker,
- Patricia A. Peyser,
- Lawrence F. Bielak,
- Jennifer A. Smith,
- Stella Aslibekyan,
- Bertha A. Hidalgo,
- Donna K. Arnett,
- Marguerite R. Irvin,
- James G. Wilson,
- Solomon K. Musani,
- Adolfo Correa,
- Stephen S. Rich,
- Xiuqing Guo,
- Jerome I. Rotter,
- Barbara A. Konkle,
- Jill M. Johnsen,
- Allison E. Ashley-Koch,
- Marilyn J. Telen,
- Vivien A. Sheehan,
- John Blangero,
- Joanne E. Curran,
- Juan M. Peralta,
- Courtney Montgomery,
- Wayne H-H Sheu,
- Ren-Hua Chung,
- Karen Schwander,
- Seyed M. Nouraie,
- Victor R. Gordeuk,
- Yingze Zhang,
- Charles Kooperberg,
- Alexander P. Reiner,
- Rebecca D. Jackson,
- Eugene R. Bleecker,
- Deborah A. Meyers,
- Xingnan Li,
- Sayantan Das,
- Ketian Yu,
- Jonathon LeFaive,
- Albert Smith,
- Tom Blackwell,
- Daniel Taliun,
- Sebastian Zollner,
- Lukas Forer,
- Sebastian Schoenherr,
- Christian Fuchsberger,
- Anita Pandit,
- Matthew Zawistowski,
- Sachin Kheterpal,
- Chad M. Brummett,
- Pradeep Natarajan,
- David Schlessinger,
- Seunggeun Lee,
- Hyun Min Kang,
- Francesco Cucca,
- Oddgeir L. Holmen,
- Bjørn O. Åsvold,
- Michael Boehnke,
- Sekar Kathiresan,
- Goncalo R. Abecasis,
- Y. Eugene Chen,
- Cristen J. Willer,
- Kristian Hveem
Affiliations
- Jonas B. Nielsen
- Department of Internal Medicine: Cardiology, University of Michigan
- Oren Rom
- Department of Internal Medicine: Cardiology, University of Michigan
- Ida Surakka
- Department of Internal Medicine: Cardiology, University of Michigan
- Sarah E. Graham
- Department of Internal Medicine: Cardiology, University of Michigan
- Wei Zhou
- Program in Medical and Population Genetics, Broad Institute of Harvard and MIT
- Tanmoy Roychowdhury
- Department of Internal Medicine: Cardiology, University of Michigan
- Lars G. Fritsche
- Department of Internal Medicine: Cardiology, University of Michigan
- Sarah A. Gagliano Taliun
- Department of Biostatistics, University of Michigan School of Public Health
- Carlo Sidore
- Istituto di Ricerca Genetica e Biomedica, Consiglio Nazionale delle Ricerche (CNR)
- Yuhao Liu
- Department of Internal Medicine: Cardiology, University of Michigan
- Maiken E. Gabrielsen
- K.G. Jebsen Center for Genetic Epidemiology, Department of Public Health and Nursing, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology, NTNU
- Anne Heidi Skogholt
- K.G. Jebsen Center for Genetic Epidemiology, Department of Public Health and Nursing, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology, NTNU
- Brooke Wolford
- Department of Internal Medicine: Cardiology, University of Michigan
- William Overton
- Department of Biostatistics, University of Michigan School of Public Health
- Ying Zhao
- Department of Internal Medicine: Cardiology, University of Michigan
- Jin Chen
- Department of Internal Medicine: Cardiology, University of Michigan
- He Zhang
- Department of Internal Medicine: Cardiology, University of Michigan
- Whitney E. Hornsby
- Department of Internal Medicine: Cardiology, University of Michigan
- Akua Acheampong
- Department of Internal Medicine: Cardiology, University of Michigan
- Austen Grooms
- Department of Internal Medicine: Cardiology, University of Michigan
- Amanda Schaefer
- Department of Human Genetics, University of Michigan
- Gregory J. M. Zajac
- Department of Biostatistics, University of Michigan School of Public Health
- Luis Villacorta
- Department of Internal Medicine: Cardiology, University of Michigan
- Jifeng Zhang
- Department of Internal Medicine: Cardiology, University of Michigan
- Ben Brumpton
- K.G. Jebsen Center for Genetic Epidemiology, Department of Public Health and Nursing, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology, NTNU
- Mari Løset
- K.G. Jebsen Center for Genetic Epidemiology, Department of Public Health and Nursing, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology, NTNU
- Vivek Rai
- Department of Computational Medicine and Bioinformatics, University of Michigan
- Pia R. Lundegaard
- Laboratory for Molecular Cardiology, Department of Cardiology, Centre for Cardiac, Vascular, Pulmonary and Infectious Diseases, Copenhagen University Hospital Rigshospitalet
- Morten S. Olesen
- Laboratory for Molecular Cardiology, Department of Cardiology, Centre for Cardiac, Vascular, Pulmonary and Infectious Diseases, Copenhagen University Hospital Rigshospitalet
- Kent D. Taylor
- The Institute for Translational Genomics and Population Sciences, Department of Pediatrics and Los Angeles Biomedical Research Institute, Harbor-UCLA
- Nicholette D. Palmer
- Department of Biochemistry, Wake Forest School of Medicine
- Yii-Der Chen
- The Institute for Translational Genomics and Population Sciences, Department of Pediatrics and Los Angeles Biomedical Research Institute, Harbor-UCLA
- Seung H. Choi
- Program in Medical and Population Genetics, Broad Institute of Harvard and MIT
- Steven A. Lubitz
- Program in Medical and Population Genetics, Broad Institute of Harvard and MIT
- Patrick T. Ellinor
- Program in Medical and Population Genetics, Broad Institute of Harvard and MIT
- Kathleen C. Barnes
- Colorado Center for Personalized Medicine, School of Medicine, University of Colorado
- Michelle Daya
- Colorado Center for Personalized Medicine, School of Medicine, University of Colorado
- Nicholas Rafaels
- Colorado Center for Personalized Medicine, School of Medicine, University of Colorado
- Scott T. Weiss
- Channing Division of Network Medicine, Department of Medicine Brigham and Women’s Hospital
- Jessica Lasky-Su
- Channing Division of Network Medicine, Department of Medicine Brigham and Women’s Hospital
- Russell P. Tracy
- Department of Pathology and Laboratory Medicine, Larner College of Medicine, University of Vermont
- Ramachandran S. Vasan
- Department of Medicine, Boston University School of Medicine
- L. Adrienne Cupples
- Framingham Heart Study
- Rasika A. Mathias
- GeneSTAR Research Program, Department of Medicine, Johns Hopkins School of Medicine
- Lisa R. Yanek
- GeneSTAR Research Program, Department of Medicine, Johns Hopkins School of Medicine
- Lewis C. Becker
- GeneSTAR Research Program, Department of Medicine, Johns Hopkins School of Medicine
- Patricia A. Peyser
- Department of Epidemiology, School of Public Health, University of Michigan
- Lawrence F. Bielak
- Department of Epidemiology, School of Public Health, University of Michigan
- Jennifer A. Smith
- Department of Epidemiology, School of Public Health, University of Michigan
- Stella Aslibekyan
- The University of Alabama at Birmingham
- Bertha A. Hidalgo
- The University of Alabama at Birmingham
- Donna K. Arnett
- Deans Office, College of Public Health, University of Kentucky
- Marguerite R. Irvin
- The University of Alabama at Birmingham
- James G. Wilson
- Department of Physiology and Biophysics, University of Mississippi Medical Center
- Solomon K. Musani
- Jackson Heart Study
- Adolfo Correa
- Jackson Heart Study
- Stephen S. Rich
- Center for Public Health Genomics, University of Virginia
- Xiuqing Guo
- The Institute for Translational Genomics and Population Sciences, Department of Pediatrics and Los Angeles Biomedical Research Institute, Harbor-UCLA
- Jerome I. Rotter
- The Institute for Translational Genomics and Population Sciences, Department of Pediatrics and Los Angeles Biomedical Research Institute, Harbor-UCLA
- Barbara A. Konkle
- BloodWorks Northwest, University of Washington
- Jill M. Johnsen
- BloodWorks Northwest, University of Washington
- Allison E. Ashley-Koch
- Duke Molecular Physiology Institute, Duke University Medical Center
- Marilyn J. Telen
- Department of Medicine, Duke University Medical Center
- Vivien A. Sheehan
- Department of Pediatrics, Division of Hematology/Oncology, Baylor College of Medicine
- John Blangero
- Department of Human Genetics, University of Texas Rio Grande Valley School of Medicine
- Joanne E. Curran
- Department of Human Genetics, University of Texas Rio Grande Valley School of Medicine
- Juan M. Peralta
- Department of Human Genetics, University of Texas Rio Grande Valley School of Medicine
- Courtney Montgomery
- Department of Genes and Human Disease, Oklahoma Medical Research Foundation
- Wayne H-H Sheu
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Taichung Veterans General Hospital
- Ren-Hua Chung
- Institute of Population Health Sciences, National Health Research Institutes
- Karen Schwander
- Division of Biostatistics, Washington University School of Medicine
- Seyed M. Nouraie
- University of Pittsburgh School of Medicine
- Victor R. Gordeuk
- University of Illinois at Chicago
- Yingze Zhang
- University of Pittsburgh School of Medicine
- Charles Kooperberg
- Division of Public Health Sciences, Fred Hutchinson Cancer Research Center
- Alexander P. Reiner
- Division of Public Health Sciences, Fred Hutchinson Cancer Research Center
- Rebecca D. Jackson
- Division of Endocrinology, Diabetes and Metabolism, Ohio State University
- Eugene R. Bleecker
- Division of Pharmacogenomics University of Arizona
- Deborah A. Meyers
- Division of Pharmacogenomics University of Arizona
- Xingnan Li
- Division of Genetics, Genomics and Precision Medicine, Department of Medicine, University of Arizona
- Sayantan Das
- Department of Computational Medicine and Bioinformatics, University of Michigan
- Ketian Yu
- Department of Biostatistics, University of Michigan School of Public Health
- Jonathon LeFaive
- Department of Biostatistics, University of Michigan School of Public Health
- Albert Smith
- Department of Biostatistics, University of Michigan School of Public Health
- Tom Blackwell
- Department of Biostatistics, University of Michigan School of Public Health
- Daniel Taliun
- Department of Biostatistics, University of Michigan School of Public Health
- Sebastian Zollner
- Department of Biostatistics, University of Michigan School of Public Health
- Lukas Forer
- Division of Genetics, Genomics and Precision Medicine, Department of Medicine, University of Arizona
- Sebastian Schoenherr
- Institute of Genetic Epidemiology, Department of Genetics and Pharmacology, Medical University of Innsbruck
- Christian Fuchsberger
- Department of Biostatistics, University of Michigan School of Public Health
- Anita Pandit
- Department of Biostatistics, University of Michigan School of Public Health
- Matthew Zawistowski
- Department of Biostatistics, University of Michigan School of Public Health
- Sachin Kheterpal
- Department of Anesthesiology, University of Michigan
- Chad M. Brummett
- Department of Anesthesiology, University of Michigan
- Pradeep Natarajan
- Program in Medical and Population Genetics, Broad Institute of Harvard and MIT
- David Schlessinger
- Laboratory of Genetics, National Institute on Aging, US National Institutes of Health
- Seunggeun Lee
- Department of Biostatistics, University of Michigan School of Public Health
- Hyun Min Kang
- Department of Biostatistics, University of Michigan School of Public Health
- Francesco Cucca
- Istituto di Ricerca Genetica e Biomedica, Consiglio Nazionale delle Ricerche (CNR)
- Oddgeir L. Holmen
- K.G. Jebsen Center for Genetic Epidemiology, Department of Public Health and Nursing, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology, NTNU
- Bjørn O. Åsvold
- K.G. Jebsen Center for Genetic Epidemiology, Department of Public Health and Nursing, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology, NTNU
- Michael Boehnke
- Department of Biostatistics, University of Michigan School of Public Health
- Sekar Kathiresan
- Harvard Medical School
- Goncalo R. Abecasis
- Department of Biostatistics, University of Michigan School of Public Health
- Y. Eugene Chen
- Department of Internal Medicine: Cardiology, University of Michigan
- Cristen J. Willer
- Department of Internal Medicine: Cardiology, University of Michigan
- Kristian Hveem
- K.G. Jebsen Center for Genetic Epidemiology, Department of Public Health and Nursing, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology, NTNU
- DOI
- https://doi.org/10.1038/s41467-020-20086-3
- Journal volume & issue
-
Vol. 11,
no. 1
pp. 1 – 12
Abstract
Drugs targeting cardiovascular disease (CVD) can have negative consequences for liver function. Here, the authors combine genome wide analyses on 69,479 individuals to identify loss-of-function variants with beneficial effects on CVD-related traits without negative impacts on liver function.
