Rare genetic variants previously associated with congenital forms of long QT syndrome have little or no effect on the QT interval

Jonas Ghouse; Christian Theil Have; Peter Weeke; Jonas Bille Nielsen; Gustav Ahlberg; Marie Balslev-Harder; Emil Vincent Appel; Tea Skaaby; Søren-Peter Olesen; Niels Grarup; Allan Linneberg; Oluf Pedersen; Stig Haunsø; Jesper Hastrup Svendsen; Torben Hansen; Jørgen Kim Kanters; Morten Salling Olesen

doi:10.1093/eurheartj/ehv297

Rare genetic variants previously associated with congenital forms of long QT syndrome have little or no effect on the QT interval

Jonas Ghouse, Christian Theil Have, Peter Weeke, Jonas Bille Nielsen, Gustav Ahlberg, Marie Balslev-Harder, Emil Vincent Appel, Tea Skaaby, Søren-Peter Olesen, Niels Grarup, Allan Linneberg, Oluf Pedersen, Stig Haunsø, Jesper Hastrup Svendsen, Torben Hansen, Jørgen Kim Kanters, Morten Salling Olesen

39 Citationer (Scopus)

Abstract

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.

Originalsprog	Engelsk
Tidsskrift	European Heart Journal
Vol/bind	36
Udgave nummer	37
Sider (fra-til)	2523-9
Antal sider	7
ISSN	0195-668X
DOI	https://doi.org/10.1093/eurheartj/ehv297
Status	Udgivet - 1 okt. 2015

FN’s Verdensmål

Dette resultat bidrager til følgende verdensmål

Adgang til dokumentet

10.1093/eurheartj/ehv297

ehv297.pdfForlagets udgivne version, 184 KBLicens: CC BY

Citationsformater

Ghouse, J., Have, C. T., Weeke, P., Nielsen, J. B., Ahlberg, G., Balslev-Harder, M., Appel, E. V., Skaaby, T., Olesen, S-P., Grarup, N., Linneberg, A., Pedersen, O., Haunsø, S., Hastrup Svendsen, J., Hansen, T., Kanters, J. K., & Salling Olesen, M. (2015). Rare genetic variants previously associated with congenital forms of long QT syndrome have little or no effect on the QT interval. European Heart Journal, 36(37), 2523-9. https://doi.org/10.1093/eurheartj/ehv297

Ghouse, J, Have, CT, Weeke, P, Nielsen, JB, Ahlberg, G, Balslev-Harder, M, Appel, EV, Skaaby, T, Olesen, S-P, Grarup, N , Linneberg, A , Pedersen, O, Haunsø, S, Hastrup Svendsen, J, Hansen, T , Kanters, JK & Salling Olesen, M 2015, 'Rare genetic variants previously associated with congenital forms of long QT syndrome have little or no effect on the QT interval', European Heart Journal, bind 36, nr. 37, s. 2523-9. https://doi.org/10.1093/eurheartj/ehv297

@article{fb367ee6928345de82ec82a5efbcb8dc,

title = "Rare genetic variants previously associated with congenital forms of long QT syndrome have little or no effect on the QT interval",

abstract = "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.",

author = "Jonas Ghouse and Have, {Christian Theil} and Peter Weeke and Nielsen, {Jonas Bille} and Gustav Ahlberg and Marie Balslev-Harder and Appel, {Emil Vincent} and Tea Skaaby and S{\o}ren-Peter Olesen and Niels Grarup and Allan Linneberg and Oluf Pedersen and Stig Hauns{\o} and {Hastrup Svendsen}, Jesper and Torben Hansen and Kanters, {J{\o}rgen Kim} and {Salling Olesen}, Morten",

year = "2015",

month = oct,

day = "1",

doi = "10.1093/eurheartj/ehv297",

language = "English",

volume = "36",

pages = "2523--9",

journal = "European Heart Journal",

issn = "0195-668X",

publisher = "Oxford University Press",

number = "37",

}

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 - Nielsen, Jonas Bille

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

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 -

Rare genetic variants previously associated with congenital forms of long QT syndrome have little or no effect on the QT interval

Abstract

FN’s Verdensmål

Adgang til dokumentet

Fingeraftryk

Citationsformater