High Heritability of Ascending Aortic Diameter and Trans-ancestry Prediction of Thoracic Aortic Disease

Overview

Journal Nat Genet

Specialty Genetics

Date 2022 May 31

PMID 35637384

Authors

Catherine Tcheandjieu

Ke Xiao

Helio Tejeda

Julie A Lynch

Sanni Ruotsalainen

Tiffany Bellomo

Madhuri Palnati

Renae Judy

Derek Klarin

Rachel L Kember

Shefali Verma

Aarno Palotie

Mark Daly

Marylyn Ritchie

Daniel J Rader

Manuel A Rivas

Themistocles Assimes

Philip Tsao

Scott Damrauer

James R Priest

Affiliations

Soon will be listed here.

Abstract

Enlargement of the aorta is an important risk factor for aortic aneurysm and dissection, a leading cause of morbidity in the developed world. Here we performed automated extraction of ascending aortic diameter from cardiac magnetic resonance images of 36,021 individuals from the UK Biobank, followed by genome-wide association. We identified lead variants across 41 loci, including genes related to cardiovascular development (HAND2, TBX20) and Mendelian forms of thoracic aortic disease (ELN, FBN1). A polygenic score significantly predicted prevalent risk of thoracic aortic aneurysm and the need for surgical intervention for patients with thoracic aneurysm across multiple ancestries within the UK Biobank, FinnGen, the Penn Medicine Biobank and the Million Veterans Program (MVP). Additionally, we highlight the primary causal role of blood pressure in reducing aortic dilation using Mendelian randomization. Overall, our findings provide a roadmap for using genetic determinants of human anatomy to understand cardiovascular development while improving prediction of diseases of the thoracic aorta.

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