Nature Communications (Aug 2022)
Endophenotype effect sizes support variant pathogenicity in monogenic disease susceptibility genes
- Jennifer L. Halford,
- Valerie N. Morrill,
- Seung Hoan Choi,
- Sean J. Jurgens,
- Giorgio Melloni,
- Nicholas A. Marston,
- Lu-Chen Weng,
- Victor Nauffal,
- Amelia W. Hall,
- Sophia Gunn,
- Christina A. Austin-Tse,
- James P. Pirruccello,
- Shaan Khurshid,
- Heidi L. Rehm,
- Emelia J. Benjamin,
- Eric Boerwinkle,
- Jennifer A. Brody,
- Adolfo Correa,
- Brandon K. Fornwalt,
- Namrata Gupta,
- Christopher M. Haggerty,
- Stephanie Harris,
- Susan R. Heckbert,
- Charles C. Hong,
- Charles Kooperberg,
- Henry J. Lin,
- Ruth J. F. Loos,
- Braxton D. Mitchell,
- Alanna C. Morrison,
- Wendy Post,
- Bruce M. Psaty,
- Susan Redline,
- Kenneth M. Rice,
- Stephen S. Rich,
- Jerome I. Rotter,
- Peter F. Schnatz,
- Elsayed Z. Soliman,
- Nona Sotoodehnia,
- Eugene K. Wong,
- NHLBI Trans-Omics for Precision Medicine (TOPMed) Consortium,
- Marc S. Sabatine,
- Christian T. Ruff,
- Kathryn L. Lunetta,
- Patrick T. Ellinor,
- Steven A. Lubitz
Affiliations
- Jennifer L. Halford
- Cardiovascular Disease Initiative, Broad Institute of MIT and Harvard
- Valerie N. Morrill
- Cardiovascular Disease Initiative, Broad Institute of MIT and Harvard
- Seung Hoan Choi
- Cardiovascular Disease Initiative, Broad Institute of MIT and Harvard
- Sean J. Jurgens
- Cardiovascular Disease Initiative, Broad Institute of MIT and Harvard
- Giorgio Melloni
- TIMI Study Group, Division of Cardiovascular Medicine, Brigham and Women’s Hospital
- Nicholas A. Marston
- TIMI Study Group, Division of Cardiovascular Medicine, Brigham and Women’s Hospital
- Lu-Chen Weng
- Cardiovascular Disease Initiative, Broad Institute of MIT and Harvard
- Victor Nauffal
- Cardiovascular Disease Initiative, Broad Institute of MIT and Harvard
- Amelia W. Hall
- Gene Regulation Observatory and Epigenomics Platform, Broad Institute of MIT and Harvard
- Sophia Gunn
- Department of Biostatistics, Boston University School of Public Health
- Christina A. Austin-Tse
- Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine
- James P. Pirruccello
- Cardiovascular Disease Initiative, Broad Institute of MIT and Harvard
- Shaan Khurshid
- Cardiovascular Disease Initiative, Broad Institute of MIT and Harvard
- Heidi L. Rehm
- Cardiovascular Disease Initiative, Broad Institute of MIT and Harvard
- Emelia J. Benjamin
- NHLBI and Boston University’s Framingham Heart Study
- Eric Boerwinkle
- Human Genetics Center, Department of Epidemiology, Human Genetics, and Environmental Sciences, School of Public Health, The University of Texas Health Science Center at Houston
- Jennifer A. Brody
- Cardiovascular Health Research Unit, Department of Medicine, University of Washington
- Adolfo Correa
- Departments of Medicine, Pediatrics and Population Health Science, University of Mississippi Medical Center
- Brandon K. Fornwalt
- Department of Translational Data Science and Informatics, Geisinger
- Namrata Gupta
- Cardiovascular Disease Initiative, Broad Institute of MIT and Harvard
- Christopher M. Haggerty
- Department of Translational Data Science and Informatics, Geisinger
- Stephanie Harris
- Cardiovascular Research Center, Massachusetts General Hospital
- Susan R. Heckbert
- Cardiovascular Health Research Unit, Department of Medicine, University of Washington
- Charles C. Hong
- University of Maryland School of Medicine
- Charles Kooperberg
- Division of Public Health Sciences, Fred Hutchinson Cancer Center
- Henry J. Lin
- The Institute for Translational Genomics and Population Sciences, Department of Pediatrics, The Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center
- Ruth J. F. Loos
- The Charles Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai
- Braxton D. Mitchell
- University of Maryland School of Medicine
- Alanna C. Morrison
- Human Genetics Center, Department of Epidemiology, Human Genetics, and Environmental Sciences, School of Public Health, The University of Texas Health Science Center at Houston
- Wendy Post
- Division of Cardiology, Johns Hopkins Medicine
- Bruce M. Psaty
- Cardiovascular Health Research Unit, Department of Medicine, University of Washington
- Susan Redline
- Department of Medicine, Brigham and Women’s Hospital
- Kenneth M. Rice
- Department of Biostatistics, University of Washington
- Stephen S. Rich
- Center for Public Health Genomics, Department of Public Health Sciences, University of Virginia
- Jerome I. Rotter
- The Institute for Translational Genomics and Population Sciences, Department of Pediatrics, The Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center
- Peter F. Schnatz
- Department of ObGyn, The Reading Hospital of Tower Health
- Elsayed Z. Soliman
- Epidemiological Cardiology Research Center, Wake Forest School of Medicine
- Nona Sotoodehnia
- Cardiovascular Health Research Unit, Department of Medicine, University of Washington
- Eugene K. Wong
- Cardiovascular Research Center, Massachusetts General Hospital
- NHLBI Trans-Omics for Precision Medicine (TOPMed) Consortium
- Marc S. Sabatine
- TIMI Study Group, Division of Cardiovascular Medicine, Brigham and Women’s Hospital
- Christian T. Ruff
- TIMI Study Group, Division of Cardiovascular Medicine, Brigham and Women’s Hospital
- Kathryn L. Lunetta
- Department of Biostatistics, Boston University School of Public Health
- Patrick T. Ellinor
- Cardiovascular Disease Initiative, Broad Institute of MIT and Harvard
- Steven A. Lubitz
- Cardiovascular Disease Initiative, Broad Institute of MIT and Harvard
- DOI
- https://doi.org/10.1038/s41467-022-32009-5
- Journal volume & issue
-
Vol. 13,
no. 1
pp. 1 – 11
Abstract
Accurate classification of genetic variants is critical for research and patient care. Here, the authors report that population-based associations between rare variants and quantitative endophenotypes for monogenic diseases can provide support for variant pathogenicity.
