PT  - JOURNAL ARTICLE
AU  - Joeri A Jansweijer
AU  - Karin Y van Spaendonck-Zwarts
AU  - Michael W T Tanck
AU  - J Peter van Tintelen
AU  - Imke Christiaans
AU  - Jasper J van der Smagt
AU  - Alexa M C Vermeer
AU  - J Martijn Bos
AU  - Arthur J Moss
AU  - Heikki Swan
AU  - Sylvia G Priori
AU  - Annika Rydberg
AU  - Jacob Tfelt-Hansen
AU  - Michael J Ackerman
AU  - Iacopo Olivotto
AU  - Philippe Charron
AU  - Juan R Gimeno
AU  - Maarten P van den Berg
AU  - Arthur AM Wilde
AU  - Yigal M Pinto
TI  - Heritability in genetic heart disease: the role of genetic background
AID  - 10.1136/openhrt-2018-000929
DP  - 2019 May 01
TA  - Open Heart
PG  - e000929
VI  - 6
IP  - 1
4099  - http://openheart.bmj.com/content/6/1/e000929.short
4100  - http://openheart.bmj.com/content/6/1/e000929.full
SO  - Open Heart2019 May 01; 6
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.