Epistasis regulates genetic control of cardiac hypertrophy.

Journal

medRxiv : the preprint server for health sciences
Titre abrégé: medRxiv
Pays: United States
ID NLM: 101767986

Informations de publication

Date de publication:
08 Nov 2023
Historique:
pubmed: 21 11 2023
medline: 21 11 2023
entrez: 21 11 2023
Statut: epublish

Résumé

The combinatorial effect of genetic variants is often assumed to be additive. Although genetic variation can clearly interact non-additively, methods to uncover epistatic relationships remain in their infancy. We develop low-signal signed iterative random forests to elucidate the complex genetic architecture of cardiac hypertrophy. We derive deep learning-based estimates of left ventricular mass from the cardiac MRI scans of 29,661 individuals enrolled in the UK Biobank. We report epistatic genetic variation including variants close to

Identifiants

DOI: 10.1101/2023.11.06.23297858 PMID: 37987017 PMC: PMC10659487
pubmed: 37987017
doi: 10.1101/2023.11.06.23297858
pmc: PMC10659487
pii:
doi:

Types de publication

Preprint

Langues

eng

Subventions

Organisme : NHLBI NIH HHS
ID : F32 HL160067
Pays : United States
Organisme : NHLBI NIH HHS
ID : K08 HL143185
Pays : United States
Organisme : NHLBI NIH HHS
ID : L30 HL159413
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL144843
Pays : United States

Déclaration de conflit d'intérêts

Competing interests E.A.A. is a Founder of Personalis, Deepcell, Svexa, RCD Co, and Parameter Health; Advisor to Oxford Nanopore, SequenceBio, and Pacific Biosciences; and a non-executive director for AstraZeneca. C.S.W. is a consultant for Tensixteen Bio and Renovacor. V.N.P. is an SAB member for and receives research support from BioMarin, Inc, and is a consultant for Constantiam, Inc. and viz.ai. The remaining authors declare no competing interests.

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Auteurs

Qianru Wang (Q)

Division of Cardiovascular Medicine, Department of Medicine, Stanford University, Stanford, CA, USA.
ORCID: 0000-0002-7219-7522

Tiffany M Tang (TM)

Department of Statistics, University of California, Berkeley, Berkeley, CA, USA.

Nathan Youlton (N)

Division of Cardiovascular Medicine, Department of Medicine, Stanford University, Stanford, CA, USA.

Chad S Weldy (CS)

Division of Cardiovascular Medicine, Department of Medicine, Stanford University, Stanford, CA, USA.
ORCID: 0000-0003-4652-6422

Ana M Kenney (AM)

Department of Statistics, University of California, Berkeley, Berkeley, CA, USA.

Omer Ronen (O)

Department of Statistics, University of California, Berkeley, Berkeley, CA, USA.

J Weston Hughes (JW)

Division of Cardiovascular Medicine, Department of Medicine, Stanford University, Stanford, CA, USA.

Elizabeth T Chin (ET)

Division of Cardiovascular Medicine, Department of Medicine, Stanford University, Stanford, CA, USA.

Shirley C Sutton (SC)

Division of Cardiovascular Medicine, Department of Medicine, Stanford University, Stanford, CA, USA.

Abhineet Agarwal (A)

Department of Statistics, University of California, Berkeley, Berkeley, CA, USA.

Xiao Li (X)

Department of Statistics, University of California, Berkeley, Berkeley, CA, USA.

Merle Behr (M)

Faculty of Informatics and Data Science, University of Regensburg, Regensburg, Germany.

Karl Kumbier (K)

Department of Pharmaceutical Chemistry, University of California, San Francisco, San Francisco, CA, USA.

Christine S Moravec (CS)

Department of Cardiovascular and Metabolic Sciences, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA.

W H Wilson Tang (WHW)

Department of Cardiovascular and Metabolic Sciences, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA.
Department of Cardiovascular Medicine, Heart Vascular and Thoracic Institute, Cleveland Clinic, Cleveland, OH, USA.

Kenneth B Margulies (KB)

Division of Cardiovascular Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Hospital of The University of Pennsylvania, Philadelphia, PA, USA.

Thomas P Cappola (TP)

Division of Cardiovascular Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Hospital of The University of Pennsylvania, Philadelphia, PA, USA.

Atul J Butte (AJ)

Bakar Computational Health Sciences Institute, University of California, San Francisco, San Francisco, CA, USA.
Chan Zuckerberg Biohub - San Francisco, San Francisco, CA, USA.

Rima Arnaout (R)

Bakar Computational Health Sciences Institute, University of California, San Francisco, San Francisco, CA, USA.
Chan Zuckerberg Biohub - San Francisco, San Francisco, CA, USA.

James B Brown (JB)

Department of Statistics, University of California, Berkeley, Berkeley, CA, USA.
Chan Zuckerberg Biohub - San Francisco, San Francisco, CA, USA.
Division of Environmental Genomics and Systems Biology, Lawrence Berkeley National Laboratory, Berkeley, CA, USA.

James R Priest (JR)

Division of Cardiovascular Medicine, Department of Medicine, Stanford University, Stanford, CA, USA.
Chan Zuckerberg Biohub - San Francisco, San Francisco, CA, USA.
Tenaya Therapeutics, San Francisco, CA, USA.
ORCID: 0000-0002-8349-4784

Victoria N Parikh (VN)

Division of Cardiovascular Medicine, Department of Medicine, Stanford University, Stanford, CA, USA.

Bin Yu (B)

Department of Statistics, University of California, Berkeley, Berkeley, CA, USA.
Chan Zuckerberg Biohub - San Francisco, San Francisco, CA, USA.
Department of Electrical Engineering and Computer Science, University of California, Berkeley, Berkeley, CA, USA.
Center for Computational Biology, University of California, Berkeley, Berkeley, CA, USA.

Euan A Ashley (EA)

Division of Cardiovascular Medicine, Department of Medicine, Stanford University, Stanford, CA, USA.
Chan Zuckerberg Biohub - San Francisco, San Francisco, CA, USA.

Classifications MeSH