TY - JOUR
T1 - Rare genetic variants previously associated with congenital forms of long QT syndrome have little or no effect on the QT interval
AU - Ghouse, Jonas
AU - Have, Christian Theil
AU - Weeke, Peter
AU - Bille Nielsen, Jonas
AU - Ahlberg, Gustav
AU - Balslev-Harder, Marie
AU - Appel, Emil Vincent
AU - Skaaby, Tea
AU - Olesen, Søren-Peter
AU - Grarup, Niels
AU - Linneberg, Allan
AU - Pedersen, Oluf
AU - Haunsø, Stig
AU - Hastrup Svendsen, Jesper
AU - Hansen, Torben
AU - Kanters, Jørgen Kim
AU - Salling Olesen, Morten
N1 - Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2015. For permissions please email: [email protected].
PY - 2015/10/1
Y1 - 2015/10/1
N2 - AIMS: We studied whether variants previously associated with congenital long QT syndrome (cLQTS) have an effect on the QTc interval in a Danish population sample. Furthermore, we assessed whether carriers of variants in cLQTS-associated genes are more prone to experience syncope compared with non-carriers and whether carriers have an increased mortality compared with non-carriers.METHODS AND RESULTS: All genetic variants previously associated with cLQTS were surveyed using the Human Gene Mutation Database. We screened a Danish population-based sample with available whole-exome sequencing data (n = 870) and genotype array data (n = 6161) for putative cLQTS genetic variants. In total, 33 of 1358 variants previously reported to associate with cLQTS were identified. Of these, 10 variants were found in 8 or more individuals. Electrocardiogram results showed normal mean QTc intervals in carriers compared with non-carriers. Syncope data analysis between variant and non-variant carriers showed that 4 of 227 (1.8%) and 95 of 5861 (1.6%) individuals, respectively, had experienced syncope during follow-up (P = 0.80). There was no significant difference in overall mortality rates between carriers [7/217 (3.2%)] and non-carriers [301/6453 (4.7%)] (P = 0.24).CONCLUSION: We present QTc data and register data, indicating that 26 cLQTS-associated variants neither had any effect on the QTc intervals nor on syncope propensity or overall mortality. Based on the frequency of individual gene variants, we suggest that the 10 variants frequently identified, assumed to relate to cLQTS, are less likely to associate with a dominant monogenic form of the disease.
AB - AIMS: We studied whether variants previously associated with congenital long QT syndrome (cLQTS) have an effect on the QTc interval in a Danish population sample. Furthermore, we assessed whether carriers of variants in cLQTS-associated genes are more prone to experience syncope compared with non-carriers and whether carriers have an increased mortality compared with non-carriers.METHODS AND RESULTS: All genetic variants previously associated with cLQTS were surveyed using the Human Gene Mutation Database. We screened a Danish population-based sample with available whole-exome sequencing data (n = 870) and genotype array data (n = 6161) for putative cLQTS genetic variants. In total, 33 of 1358 variants previously reported to associate with cLQTS were identified. Of these, 10 variants were found in 8 or more individuals. Electrocardiogram results showed normal mean QTc intervals in carriers compared with non-carriers. Syncope data analysis between variant and non-variant carriers showed that 4 of 227 (1.8%) and 95 of 5861 (1.6%) individuals, respectively, had experienced syncope during follow-up (P = 0.80). There was no significant difference in overall mortality rates between carriers [7/217 (3.2%)] and non-carriers [301/6453 (4.7%)] (P = 0.24).CONCLUSION: We present QTc data and register data, indicating that 26 cLQTS-associated variants neither had any effect on the QTc intervals nor on syncope propensity or overall mortality. Based on the frequency of individual gene variants, we suggest that the 10 variants frequently identified, assumed to relate to cLQTS, are less likely to associate with a dominant monogenic form of the disease.
U2 - 10.1093/eurheartj/ehv297
DO - 10.1093/eurheartj/ehv297
M3 - Journal article
C2 - 26159999
SN - 0195-668X
VL - 36
SP - 2523
EP - 2529
JO - European Heart Journal
JF - European Heart Journal
IS - 37
ER -