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

Y1 - 2019

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.

U2 - 10.1136/openhrt-2018-000929

DO - 10.1136/openhrt-2018-000929

M3 - Journal article

C2 - 31245010

VL - 6

SP - 1

EP - 6

JO - Open Heart

JF - Open Heart

SN - 2398-595X

IS - 1

M1 - e000929

ER -