학술논문
High heritability of ascending aortic diameter and trans-ancestry prediction of thoracic aortic disease
Document Type
Article
Author
Tcheandjieu, Catherine; Xiao, Ke; Tejeda, Helio; Lynch, Julie A.; Ruotsalainen, Sanni; Bellomo, Tiffany; Palnati, Madhuri; Judy, Renae; Klarin, Derek; Kember, Rachel L.; Verma, Shefali; Palotie, Aarno; Daly, Mark; Ritchie, Marylyn; Rader, Daniel J.; Rivas, Manuel A.; Assimes, Themistocles; Tsao, Philip; Damrauer, Scott; Priest, James R.
Source
Nature Genetics; June 2022, Vol. 54 Issue: 6 p772-782, 11p
Subject
Language
ISSN
10614036; 15461718
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.