Nature Communications (Aug 2020)
Polygenic background modifies penetrance of monogenic variants for tier 1 genomic conditions
- Akl C. Fahed,
- Minxian Wang,
- Julian R. Homburger,
- Aniruddh P. Patel,
- Alexander G. Bick,
- Cynthia L. Neben,
- Carmen Lai,
- Deanna Brockman,
- Anthony Philippakis,
- Patrick T. Ellinor,
- Christopher A. Cassa,
- Matthew Lebo,
- Kenney Ng,
- Eric S. Lander,
- Alicia Y. Zhou,
- Sekar Kathiresan,
- Amit V. Khera
Affiliations
- Akl C. Fahed
- Center for Genomic Medicine, Department of Medicine, Massachusetts General Hospital
- Minxian Wang
- Cardiovascular Disease Initiative, Broad Institute of MIT and Harvard
- Julian R. Homburger
- Color Genomics
- Aniruddh P. Patel
- Center for Genomic Medicine, Department of Medicine, Massachusetts General Hospital
- Alexander G. Bick
- Center for Genomic Medicine, Department of Medicine, Massachusetts General Hospital
- Cynthia L. Neben
- Color Genomics
- Carmen Lai
- Color Genomics
- Deanna Brockman
- Center for Genomic Medicine, Department of Medicine, Massachusetts General Hospital
- Anthony Philippakis
- Cardiovascular Disease Initiative, Broad Institute of MIT and Harvard
- Patrick T. Ellinor
- Division of Cardiology, Department of Medicine, Massachusetts General Hospital
- Christopher A. Cassa
- Division of Genetics, Brigham and Women’s Hospital, Harvard Medical School
- Matthew Lebo
- Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine
- Kenney Ng
- Center for Computational Health, IBM Research
- Eric S. Lander
- Cardiovascular Disease Initiative, Broad Institute of MIT and Harvard
- Alicia Y. Zhou
- Color Genomics
- Sekar Kathiresan
- Division of Cardiology, Department of Medicine, Massachusetts General Hospital
- Amit V. Khera
- Center for Genomic Medicine, Department of Medicine, Massachusetts General Hospital
- DOI
- https://doi.org/10.1038/s41467-020-17374-3
- Journal volume & issue
-
Vol. 11,
no. 1
pp. 1 – 9
Abstract
Genetic variation predisposes to disease via monogenic and polygenic risk variants. Here, the authors assess the interplay between these types of variation on disease penetrance in 80,928 individuals. In carriers of monogenic variants, they show that disease risk is a gradient influenced by polygenic background.
