Genome-wide Association Analysis Reveals Insights into the Genetic Architecture of Right Ventricular Structure and Function

Overview

Journal Nat Genet

Specialty Genetics

Date 2022 Jun 13

PMID 35697868

Authors

Nay Aung

Jose D Vargas

Chaojie Yang

Kenneth Fung

Mihir M Sanghvi

Stefan K Piechnik

Stefan Neubauer

Ani Manichaikul

Jerome I Rotter

Kent D Taylor

Joao A C Lima

David A Bluemke

Steven M Kawut

Steffen E Petersen

Patricia B Munroe

Affiliations

Soon will be listed here.

Abstract

Right ventricular (RV) structure and function influence the morbidity and mortality from coronary artery disease (CAD), dilated cardiomyopathy (DCM), pulmonary hypertension and heart failure. Little is known about the genetic basis of RV measurements. Here we perform genome-wide association analyses of four clinically relevant RV phenotypes (RV end-diastolic volume, RV end-systolic volume, RV stroke volume, RV ejection fraction) from cardiovascular magnetic resonance images, using a state-of-the-art deep learning algorithm in 29,506 UK Biobank participants. We identify 25 unique loci associated with at least one RV phenotype at P < 2.27 ×10, 17 of which are validated in a combined meta-analysis (n = 41,830). Several candidate genes overlap with Mendelian cardiomyopathy genes and are involved in cardiac muscle contraction and cellular adhesion. The RV polygenic risk scores (PRSs) are associated with DCM and CAD. The findings substantially advance our understanding of the genetic underpinning of RV measurements.

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