Shared genetic pathways contribute to risk of hypertrophic and dilated cardiomyopathies with opposite directions of effect
- Tadros, Rafik
- Francis, Catherine
- Xu, Xiao
- Vermeer, Alexa M. C.
- Harper, Andrew R.
- Huurman, Roy
- Bisabu, Ken Kelu
- Walsh, Roddy
- Hoorntje, Edgar T.
- te Rijdt, Wouter P.
- Buchan, Rachel J.
- van Velzen, Hannah G.
- van Slegtenhorst, Marjon A.
- Vermeulen, Jentien M.
- Offerhaus, Joost Allard
- Bai, Wenjia
- de Marvao, Antonio
- Lahrouchi, Najim
- Beekman, Leander
- Karper, Jacco C.
- Veldink, Jan H.
- Kayvanpour, Elham
- Pantazis, Antonis
- Baksi, A. John
- Whiffin, Nicola
- Mazzarotto, Francesco
- Sloane, Geraldine
- Suzuki, Hideaki
- Schneider-Luftman, Deborah
- Elliott, Paul
- Richard, Pascale
- Ader, Flavie
- Villard, Eric
- Lichtner, Peter
- Meitinger, Thomas
- Tanck, Michael W. T.
- van Tintelen, J. Peter
- Thain, Andrew
- McCarty, David
- Hegele, Robert A.
- Roberts, Jason D.
- Amyot, Julie
- Dube, Marie-Pierre
- Cadrin-Tourigny, Julia
- Giraldeau, Genevieve
- L'Allier, Philippe L.
- Garceau, Patrick
- Tardif, Jean-Claude
- Boekholdt, S. Matthijs
- Lumbers, R. Thomas
- Asselbergs, Folkert W.
- Barton, Paul J. R.
- Cook, Stuart A.
- Prasad, Sanjay K.
- O'Regan, Declan P.
- van der Velden, Jolanda
- Verweij, Karin J. H.
- Talajic, Mario
- Lettre, Guillaume
- Pinto, Yigal M.
- Meder, Benjamin
- Charron, Philippe
- de Boer, Rudolf A.
- Christiaans, Imke
- Michels, Michelle
- Wilde, Arthur A. M.
- Watkins, Hugh
- Matthews, Paul M.
- Ware, James S.
- Bezzina, Connie R.
DOIAbstract
The heart muscle diseases hypertrophic (HCM) and dilated (DCM) cardiomyopathies are leading causes of sudden death and heart failure in young, otherwise healthy, individuals. We conducted genome-wide association studies and multi-trait analyses in HCM (1,733 cases), DCM (5,521 cases) and nine left ventricular (LV) traits (19,260 UK Biobank participants with structurally normal hearts). We identified 16 loci associated with HCM, 13 with DCM and 23 with LV traits. We show strong genetic correlations between LV traits and cardiomyopathies, with opposing effects in HCM and DCM. Two-sample Mendelian randomization supports a causal association linking increased LV contractility with HCM risk. A polygenic risk score explains a significant portion ...
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