TY - JOUR
T1 - High heritability of ascending aortic diameter and trans-ancestry prediction of thoracic aortic disease
AU - FinnGen Project
AU - Regeneron Genetics Center
AU - Research Program Management & Strategic Initiatives
AU - Analytical Genomics and Data Science
AU - Genome Informatics
AU - Clinical Informatics
AU - Sequencing and Lab Operations
AU - RGC Management and Leadership Team
AU - VA Million Veterans Program
AU - Tcheandjieu, Catherine
AU - Xiao, Ke
AU - Tejeda, Helio
AU - Lynch, Julie A.
AU - Ruotsalainen, Sanni
AU - Bellomo, Tiffany
AU - Palnati, Madhuri
AU - Judy, Renae
AU - Klarin, Derek
AU - Kember, Rachel L.
AU - Verma, Shefali
AU - Mitnaul, Lyndon J.
AU - Mighty, Jason
AU - Jones, Marcus B.
AU - Ziyatdinov, Andrey
AU - Zhang, Blair
AU - Ye, Bin
AU - Watanabe, Kyoko
AU - Stahl, Eli
AU - Sidore, Carlo
AU - Paulding, Charles
AU - Moscati, Arden
AU - Mbatchou, Joelle
AU - Marcketta, Anthony
AU - Marchini, Jonathan
AU - Locke, Adam
AU - Liu, Daren
AU - Lin, Nan
AU - Li, Alexander
AU - Kosmicki, Jack
AU - Kessler, Michael
AU - Kang, Hyun Min
AU - Jorgenson, Eric
AU - Gurski, Lauren
AU - Gillies, Christopher
AU - Ghosh, Arkopravo
AU - Ferreira, Manuel Allen Revez
AU - Dobbyn, Lee
AU - Damask, Amy
AU - Backman, Joshua
AU - Xin, Jiwen
AU - Sun, Kathie
AU - Salerno, William
AU - Rasool, Ayesha
AU - Polanco, Tommy
AU - Panea, Razvan
AU - Orelus, Max
AU - O’Keeffe, Sean
AU - Nafde, Mona
AU - Mitra, George
N1 - Publisher Copyright:
© The Author(s), under exclusive licence to Springer Nature America, Inc. 2022.
PY - 2022/6
Y1 - 2022/6
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85132452365&partnerID=8YFLogxK
U2 - 10.1038/s41588-022-01070-7
DO - 10.1038/s41588-022-01070-7
M3 - Article
C2 - 35637384
AN - SCOPUS:85132452365
SN - 1061-4036
VL - 54
SP - 772
EP - 782
JO - Nature Genetics
JF - Nature Genetics
IS - 6
ER -