RT Journal Article
SR Electronic
T1 Heritability in genetic heart disease: the role of genetic background
JF Open Heart
JO Open Heart
FD British Cardiovascular Society
SP e000929
DO 10.1136/openhrt-2018-000929
VO 6
IS 1
A1 Joeri A Jansweijer
A1 Karin Y van Spaendonck-Zwarts
A1 Michael W T Tanck
A1 J Peter van Tintelen
A1 Imke Christiaans
A1 Jasper J van der Smagt
A1 Alexa M C Vermeer
A1 J Martijn Bos
A1 Arthur J Moss
A1 Heikki Swan
A1 Sylvia G Priori
A1 Annika Rydberg
A1 Jacob Tfelt-Hansen
A1 Michael J Ackerman
A1 Iacopo Olivotto
A1 Philippe Charron
A1 Juan R Gimeno
A1 Maarten P van den Berg
A1 Arthur AM Wilde
A1 Yigal M Pinto
YR 2019
UL http://openheart.bmj.com/content/6/1/e000929.abstract
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.