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 John Ackerman, Iacopo Olivotto, Philippe Charron, Juan R. Gimeno, Maarten Van Den Berg, Arthur Wilde, Yigal M. Pinto

Research output: Contribution to journalArticle

Abstract

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
Volume6
Issue number1
DOIs
StatePublished - May 1 2019

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Inborn Genetic Diseases
Heart Diseases
Long QT Syndrome
Mutation
Monozygotic Twins
Cardiomyopathies
Diseases in Twins
Channelopathies
Modifier Genes
Hypertrophic Cardiomyopathy
Ion Channels
Genetic Background
Genes
Proteins

Keywords

  • Cardiomyopathy
  • Channelopathy
  • Genetics
  • Twin Study

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

Jansweijer, J. A., Van Spaendonck-Zwarts, K. Y., Tanck, M. W. T., Peter Van Tintelen, J., Christiaans, I., Van Der Smagt, J., ... Pinto, Y. M. (2019). Heritability in genetic heart disease: The role of genetic background. Open Heart, 6(1), [e000929]. https://doi.org/10.1136/openhrt-2018-000929

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

In: Open Heart, Vol. 6, No. 1, e000929, 01.05.2019.

Research output: Contribution to journalArticle

Jansweijer, JA, Van Spaendonck-Zwarts, KY, Tanck, MWT, Peter Van Tintelen, J, Christiaans, I, Van Der Smagt, J, Vermeer, A, Bos, JM, Moss, AJ, Swan, H, Priori, S, Rydberg, A, Tfelt-Hansen, J, Ackerman, MJ, Olivotto, I, Charron, P, Gimeno, JR, Van Den Berg, M, Wilde, A & Pinto, YM 2019, 'Heritability in genetic heart disease: The role of genetic background', Open Heart, vol. 6, no. 1, e000929. https://doi.org/10.1136/openhrt-2018-000929
Jansweijer JA, Van Spaendonck-Zwarts KY, Tanck MWT, Peter Van Tintelen J, Christiaans I, Van Der Smagt J et al. Heritability in genetic heart disease: The role of genetic background. Open Heart. 2019 May 1;6(1). e000929. https://doi.org/10.1136/openhrt-2018-000929
Jansweijer, Joeri A. ; Van Spaendonck-Zwarts, Karin Y. ; Tanck, Michael W.T. ; Peter Van Tintelen, J. ; Christiaans, Imke ; Van Der Smagt, Jasper ; Vermeer, Alexa ; Bos, J. Martijn ; Moss, Arthur J. ; Swan, Heikki ; Priori, Sylvia ; Rydberg, Annika ; Tfelt-Hansen, Jacob ; Ackerman, Michael John ; Olivotto, Iacopo ; Charron, Philippe ; Gimeno, Juan R. ; Van Den Berg, Maarten ; Wilde, Arthur ; Pinto, Yigal M. / Heritability in genetic heart disease : The role of genetic background. In: Open Heart. 2019 ; Vol. 6, No. 1.
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N2 - 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.

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