High heritability of ascending aortic diameter and trans-ancestry prediction of thoracic aortic disease.
Catherine TcheandjieuKe XiaoHelio TejedaJulie A LynchSanni E RuotsalainenTiffany BellomoMadhuri PalnatiRenae JudyDerek M KlarinRachel L KemberShefali Vermanull nullnull nullnull nullAarno PalotieMark DalyMarylyn DeRiggi RitchieDaniel James RaderManuel A RivasThemistocles L AssimesPhilip TsaoScott DamrauerJames R PriestPublished in: Nature genetics (2022)
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.
Keyphrases
- pulmonary artery
- aortic valve
- aortic dissection
- aortic aneurysm
- coronary artery
- spinal cord
- left ventricular
- genome wide association
- magnetic resonance
- pulmonary hypertension
- blood pressure
- pulmonary arterial hypertension
- genome wide
- deep learning
- endothelial cells
- randomized controlled trial
- copy number
- heart failure
- cross sectional
- optic nerve
- adipose tissue
- genome wide association study
- insulin resistance
- dna methylation
- optical coherence tomography
- heart rate
- metabolic syndrome