Heritability in genetic heart disease: The role of genetic background

Joeri A. Jansweijer, Karin Y. Van Spaendonck-Zwarts, Michael W.T. Tanck, J. Peter Van Tintelen, Imke Christiaans, Jasper Van Der Smagt, Alexa Vermeer, J. Martijn Bos, Arthur J. Moss, Heikki Swan, Sylvia Priori, Annika Rydberg, Jacob Tfelt-Hansen, Michael Ackerman, Iacopo Olivotto, Philippe Charron, Juan R. Gimeno, Maarten Van Den Berg, Arthur Wilde, Yigal M. Pinto

Research output: Contribution to journalArticlepeer-review

5 Scopus citations


Background Mutations in genes encoding ion channels or sarcomeric proteins are an important cause of hereditary cardiac disease. However, the severity of the resultant disease varies considerably even among those with an identical mutation. Such clinical variation is often thought to be explained largely by differences in genetic background or modifier genes'. We aimed to test the prediction that identical genetic backgrounds result in largely similar clinical expression of a cardiac disease causing mutation, by studying the clinical expression of mutations causing cardiac disease in monozygotic twins. Methods We compared first available clinical information on 46 monozygotic twin pairs and 59 control pairs that had either a hereditary cardiomyopathy or channelopathy. Results Despite limited power of this study, we found significant heritability for corrected QT interval (QTc) in long QT syndrome (LQTS). We could not detect significant heritability for structural traits, but found a significant environmental effect on thickness of the interventricular septum in hypertrophic cardiomyopathy. Conclusions Our study confirms previously found robust heritability for electrical traits like QTc in LQTS, and adds information on low or lacking heritability for structural traits in heritable cardiomyopathies. This may steer the search for genetic modifiers in heritable cardiac disease.

Original languageEnglish (US)
Article numbere000929
JournalOpen Heart
Issue number1
StatePublished - May 1 2019


  • Cardiomyopathy
  • Channelopathy
  • Genetics
  • Twin Study

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine


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