Genetic analysis of right heart structure and function in 40,000 people.
James Paul PirruccelloPaolo Di AchilleVictor NauffalMahan NekouiSamuel F FriedmanMarcus D R KlarqvistMark D ChaffinLu-Chen WangJonathan W CunninghamShaan KhurshidCarolina RoselliHonghuang LinSatoshi KoyamaShefali S VermaYoichiro KamataniIssei Komuronull nullSean Joseph JurgensEmelia J BenjaminPuneet BatraPradeep NatarajanKenney NgUdo HoffmannSteven A LubitzJennifer E HoMark E LindsayAnthony A PhilippakisPatrick T EllinorPublished in: Nature genetics (2022)
Congenital heart diseases often involve maldevelopment of the evolutionarily recent right heart chamber. To gain insight into right heart structure and function, we fine-tuned deep learning models to recognize the right atrium, right ventricle and pulmonary artery, measuring right heart structures in 40,000 individuals from the UK Biobank with magnetic resonance imaging. Genome-wide association studies identified 130 distinct loci associated with at least one right heart measurement, of which 72 were not associated with left heart structures. Loci were found near genes previously linked with congenital heart disease, including NKX2-5, TBX5/TBX3, WNT9B and GATA4. A genome-wide polygenic predictor of right ventricular ejection fraction was associated with incident dilated cardiomyopathy (hazard ratio, 1.33 per standard deviation; P = 7.1 × 10 -13 ) and remained significant after accounting for a left ventricular polygenic score. Harnessing deep learning to perform large-scale cardiac phenotyping, our results yield insights into the genetic determinants of right heart structure and function.
Keyphrases
- genome wide
- pulmonary artery
- heart failure
- deep learning
- magnetic resonance imaging
- left ventricular
- atrial fibrillation
- ejection fraction
- genome wide association
- pulmonary hypertension
- coronary artery
- dna methylation
- pulmonary arterial hypertension
- machine learning
- cardiovascular disease
- aortic stenosis
- stem cells
- computed tomography
- type diabetes
- coronary artery disease
- copy number
- acute myocardial infarction
- mass spectrometry
- percutaneous coronary intervention
- convolutional neural network
- aortic valve
- inferior vena cava
- congenital heart disease
- left atrial