Genetic analysis of right heart structure and function in 40,000 people

BioBank Japan Project, James P. Pirruccello, Paolo Di Achille, Victor Nauffal, Mahan Nekoui, Samuel F. Friedman, Marcus D. R. Klarqvist, Mark D. Chaffin, Lu-Chen Weng, Jonathan W. Cunningham, Shaan Khurshid, Carolina Roselli, Honghuang Lin, Satoshi Koyama, Kaoru Ito, Yoichiro Kamatani, Issei Komuro, Sean J. Jurgens, Emelia J. Benjamin, Puneet BatraPradeep Natarajan, Kenney Ng, Udo Hoffmann, Steven A. Lubitz, Jennifer E. Ho, Mark E. Lindsay, Anthony A. Philippakiss, Patrick T. Ellinor*

*Bijbehorende auteur voor dit werk

    OnderzoeksoutputAcademicpeer review

    1 Citaat (Scopus)


    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 x 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.

    Genome-wide analyses of cardiac magnetic resonance imaging data identify loci associated with right heart structure and function. A polygenic predictor of right ventricular ejection fraction is associated with dilated cardiomyopathy risk.

    Originele taal-2English
    Pagina's (van-tot)792-803
    Aantal pagina's18
    TijdschriftNature genetics
    Nummer van het tijdschrift6
    StatusPublished - 13-jun-2022

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