Nature Communications (Apr 2018)
Analysis of predicted loss-of-function variants in UK Biobank identifies variants protective for disease
- Connor A. Emdin,
- Amit V. Khera,
- Mark Chaffin,
- Derek Klarin,
- Pradeep Natarajan,
- Krishna Aragam,
- Mary Haas,
- Alexander Bick,
- Seyedeh M. Zekavat,
- Akihiro Nomura,
- Diego Ardissino,
- James G. Wilson,
- Heribert Schunkert,
- Ruth McPherson,
- Hugh Watkins,
- Roberto Elosua,
- Matthew J. Bown,
- Nilesh J. Samani,
- Usman Baber,
- Jeanette Erdmann,
- Namrata Gupta,
- John Danesh,
- Daniel Chasman,
- Paul Ridker,
- Joshua Denny,
- Lisa Bastarache,
- Judith H. Lichtman,
- Gail D’Onofrio,
- Jennifer Mattera,
- John A. Spertus,
- Wayne H.-H. Sheu,
- Kent D. Taylor,
- Bruce M. Psaty,
- Stephen S. Rich,
- Wendy Post,
- Jerome I. Rotter,
- Yii-Der Ida Chen,
- Harlan Krumholz,
- Danish Saleheen,
- Stacey Gabriel,
- Sekar Kathiresan
Affiliations
- Connor A. Emdin
- Center for Genomic Medicine, Massachusetts General Hospital, Harvard Medical School
- Amit V. Khera
- Center for Genomic Medicine, Massachusetts General Hospital, Harvard Medical School
- Mark Chaffin
- Center for Genomic Medicine, Massachusetts General Hospital, Harvard Medical School
- Derek Klarin
- Center for Genomic Medicine, Massachusetts General Hospital, Harvard Medical School
- Pradeep Natarajan
- Center for Genomic Medicine, Massachusetts General Hospital, Harvard Medical School
- Krishna Aragam
- Center for Genomic Medicine, Massachusetts General Hospital, Harvard Medical School
- Mary Haas
- Center for Genomic Medicine, Massachusetts General Hospital, Harvard Medical School
- Alexander Bick
- Center for Genomic Medicine, Massachusetts General Hospital, Harvard Medical School
- Seyedeh M. Zekavat
- Center for Genomic Medicine, Massachusetts General Hospital, Harvard Medical School
- Akihiro Nomura
- Center for Genomic Medicine, Massachusetts General Hospital, Harvard Medical School
- Diego Ardissino
- Division of Cardiology, Azienda Ospedaliero–Universitaria di Parma
- James G. Wilson
- Department of Physiology and Biophysics, University of Mississippi Medical Center
- Heribert Schunkert
- Deutsches Herzzentrum München, Technische Universität München, Deutsches Zentrum für Herz-Kreislauf-Forschung
- Ruth McPherson
- University of Ottawa Heart Institute
- Hugh Watkins
- Radcliffe Department of Medicine, Division of Cardiovascular Medicine, University of Oxford
- Roberto Elosua
- Cardiovascular Epidemiology and Genetics, Hospital del Mar Research Institute
- Matthew J. Bown
- Department of Cardiovascular Sciences, University of Leicester, and NIHR Leicester Biomedical Research Centre
- Nilesh J. Samani
- Department of Cardiovascular Sciences, University of Leicester, and NIHR Leicester Biomedical Research Centre
- Usman Baber
- The Zena and Michael A. Wiener Cardiovascular Institute, Icahn School of Medicine at Mount Sinai
- Jeanette Erdmann
- Institute for Integrative and Experimental Genomics, University of Lübeck
- Namrata Gupta
- Program in Medical and Population Genetics, Broad Institute
- John Danesh
- Department of Public Health and Primary Care, Cardiovascular Epidemiology Unit, University of Cambridge
- Daniel Chasman
- Center for Cardiovascular Disease Prevention, Brigham and Women’s Hospital
- Paul Ridker
- Center for Cardiovascular Disease Prevention, Brigham and Women’s Hospital
- Joshua Denny
- Department of Biomedical Informatics, Vanderbilt University
- Lisa Bastarache
- Department of Biomedical Informatics, Vanderbilt University
- Judith H. Lichtman
- Department of Chronic Disease Epidemiology, Yale School of Public Health
- Gail D’Onofrio
- Department of Emergency Medicine, Yale University
- Jennifer Mattera
- Center for Outcomes Research and Evaluation, Yale–New Haven Hospital
- John A. Spertus
- Department of Biomedical & Saint Luke’s Mid America Heart Institute and the Health Informatics, Division of Endocrinology and Metabolism, University of Missouri-Kansas City
- Wayne H.-H. Sheu
- Department of Internal Medicine, Taichung Veterans General Hospital
- Kent D. Taylor
- The Institute for Translational Genomics and Population Sciences, LABioMed and Department of Pediatrics at Harbor-UCLA Medical Center
- Bruce M. Psaty
- Cardiovascular Health Research Unit, Departments of Medicine, Epidemiology and Health Services, University of Washington
- Stephen S. Rich
- Center for Public Health Genomics, University of Virginia School of Medicine
- Wendy Post
- Division of Cardiology, Johns Hopkins University School of Medicine
- Jerome I. Rotter
- The Institute for Translational Genomics and Population Sciences, LABioMed and Department of Pediatrics at Harbor-UCLA Medical Center
- Yii-Der Ida Chen
- The Institute for Translational Genomics and Population Sciences, LABioMed and Department of Pediatrics at Harbor-UCLA Medical Center
- Harlan Krumholz
- Center for Outcomes Research and Evaluation, Yale–New Haven Hospital
- Danish Saleheen
- Center for Non-Communicable Diseases
- Stacey Gabriel
- Program in Medical and Population Genetics, Broad Institute
- Sekar Kathiresan
- Center for Genomic Medicine, Massachusetts General Hospital, Harvard Medical School
- DOI
- https://doi.org/10.1038/s41467-018-03911-8
- Journal volume & issue
-
Vol. 9,
no. 1
pp. 1 – 8
Abstract
Examination of predicted loss-of-function (pLOF) genetic variants allows direct identification of genes with therapeutic potential. Here, Emdin et al. perform association analysis for 3759 pLOF variants with 24 traits and highlight protective variants against cardiometabolic and immune phenotypes.
