TY - JOUR
T1 - Heritability in genetic heart disease
T2 - the role of genetic background
AU - Jansweijer, Joeri A.
AU - van Spaendonck-Zwarts, Karin Y.
AU - Tanck, Michael W. T.
AU - van Tintelen, J. Peter
AU - Christiaans, Imke
AU - van der Smagt, Jasper
AU - Vermeer, Alexa
AU - Bos, J. Martijn
AU - Moss, Arthur J.
AU - Swan, Heikki
AU - Priori, Sylvia
AU - Rydberg, Annika
AU - Tfelt-Hansen, Jacob
AU - Ackerman, Michael
AU - Olivotto, Iacopo
AU - Charron, Philippe
AU - Gimeno, Juan R.
AU - van den Berg, Maarten
AU - Wilde, Arthur
AU - Pinto, Yigal M.
PY - 2019/6/28
Y1 - 2019/6/28
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.
AB - 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.
KW - IDIOPATHIC DILATED CARDIOMYOPATHY
KW - LEFT-VENTRICULAR NONCOMPACTION
KW - HYPERTROPHIC CARDIOMYOPATHY
KW - QT INTERVAL
KW - MONOZYGOTIC TWINS
KW - IDENTICAL-TWINS
KW - ONSET
U2 - 10.1136/openhrt-2018-000929
DO - 10.1136/openhrt-2018-000929
M3 - Article
C2 - 31245010
SN - 2053-3624
VL - 6
JO - Open Heart
JF - Open Heart
IS - 1
M1 - 000929
ER -