Reappraisal of variants previously linked with sudden infant death syndrome: results from three population-based cohorts

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Reappraisal of variants previously linked with sudden infant death syndrome: results from three population-based cohorts. / Paludan-Mueller, Christian; Ghouse, Jonas; Vad, Oliver B.; Herfelt, Cecilie B.; Lundegaard, Pia; Ahlberg, Gustav; Schmitt, Nicole; Svendsen, Jesper H.; Haunso, Stig; Bundgaard, Henning; Hansen, Torben; Kanters, Jurgen K.; Olesen, Morten S.

I: European Journal of Human Genetics, Bind 27, Nr. 9, 2019, s. 1427-1435.

Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt

Harvard

Paludan-Mueller, C, Ghouse, J, Vad, OB, Herfelt, CB, Lundegaard, P, Ahlberg, G, Schmitt, N, Svendsen, JH, Haunso, S, Bundgaard, H, Hansen, T, Kanters, JK & Olesen, MS 2019, 'Reappraisal of variants previously linked with sudden infant death syndrome: results from three population-based cohorts', European Journal of Human Genetics, bind 27, nr. 9, s. 1427-1435. https://doi.org/10.1038/s41431-019-0416-3

APA

Paludan-Mueller, C., Ghouse, J., Vad, O. B., Herfelt, C. B., Lundegaard, P., Ahlberg, G., Schmitt, N., Svendsen, J. H., Haunso, S., Bundgaard, H., Hansen, T., Kanters, J. K., & Olesen, M. S. (2019). Reappraisal of variants previously linked with sudden infant death syndrome: results from three population-based cohorts. European Journal of Human Genetics, 27(9), 1427-1435. https://doi.org/10.1038/s41431-019-0416-3

Vancouver

Paludan-Mueller C, Ghouse J, Vad OB, Herfelt CB, Lundegaard P, Ahlberg G o.a. Reappraisal of variants previously linked with sudden infant death syndrome: results from three population-based cohorts. European Journal of Human Genetics. 2019;27(9):1427-1435. https://doi.org/10.1038/s41431-019-0416-3

Author

Paludan-Mueller, Christian ; Ghouse, Jonas ; Vad, Oliver B. ; Herfelt, Cecilie B. ; Lundegaard, Pia ; Ahlberg, Gustav ; Schmitt, Nicole ; Svendsen, Jesper H. ; Haunso, Stig ; Bundgaard, Henning ; Hansen, Torben ; Kanters, Jurgen K. ; Olesen, Morten S. / Reappraisal of variants previously linked with sudden infant death syndrome: results from three population-based cohorts. I: European Journal of Human Genetics. 2019 ; Bind 27, Nr. 9. s. 1427-1435.

Bibtex

@article{655cd16599954953bb35bf0a022881a1,
title = "Reappraisal of variants previously linked with sudden infant death syndrome: results from three population-based cohorts",
abstract = "We aimed to investigate the pathogenicity of cardiac ion channel variants previously associated with SIDS. We reviewed SIDS-associated variants previously reported in databases and the literature in three large population-based cohorts; The ExAC database, the Inter99 study, and the UK Biobank (UKBB). Variants were classified according to the American College of Medical Genetics and Genomics (ACMG) guidelines. Of the 92 SIDS-associated variants, 59 (64%) were present in ExAC, 18 (20%) in Inter99, and 24 (26%) in UKBB. Using the Inter99 cohort, we found no difference in J-point amplitude and QTc-interval between carriers and non-carriers for 14/18 variants. There was no difference in the risk of syncope (P = 0.32), malignant ventricular arrhythmia (P = 0.96), and all-cause mortality (P = 0.59) between carriers and non-carriers. The ACMG guidelines reclassified 75% of all variants as variant-of-uncertain significance, likely benign, and benign. We identified similar to 2/3 of variants previously associated with SIDS and found no significant associations with electrocardiographic traits, syncope, malignant ventricular arrhythmia, or all-cause mortality. These data indicate that many of these variants are not highly penetrant, monogenic causes of SIDS and underline the importance of frequent reappraisal of genetic variants to avoid future misdiagnosis.",
author = "Christian Paludan-Mueller and Jonas Ghouse and Vad, {Oliver B.} and Herfelt, {Cecilie B.} and Pia Lundegaard and Gustav Ahlberg and Nicole Schmitt and Svendsen, {Jesper H.} and Stig Haunso and Henning Bundgaard and Torben Hansen and Kanters, {Jurgen K.} and Olesen, {Morten S.}",
year = "2019",
doi = "10.1038/s41431-019-0416-3",
language = "English",
volume = "27",
pages = "1427--1435",
journal = "European Journal of Human Genetics",
issn = "1018-4813",
publisher = "nature publishing group",
number = "9",

}

RIS

TY - JOUR

T1 - Reappraisal of variants previously linked with sudden infant death syndrome: results from three population-based cohorts

AU - Paludan-Mueller, Christian

AU - Ghouse, Jonas

AU - Vad, Oliver B.

AU - Herfelt, Cecilie B.

AU - Lundegaard, Pia

AU - Ahlberg, Gustav

AU - Schmitt, Nicole

AU - Svendsen, Jesper H.

AU - Haunso, Stig

AU - Bundgaard, Henning

AU - Hansen, Torben

AU - Kanters, Jurgen K.

AU - Olesen, Morten S.

PY - 2019

Y1 - 2019

N2 - We aimed to investigate the pathogenicity of cardiac ion channel variants previously associated with SIDS. We reviewed SIDS-associated variants previously reported in databases and the literature in three large population-based cohorts; The ExAC database, the Inter99 study, and the UK Biobank (UKBB). Variants were classified according to the American College of Medical Genetics and Genomics (ACMG) guidelines. Of the 92 SIDS-associated variants, 59 (64%) were present in ExAC, 18 (20%) in Inter99, and 24 (26%) in UKBB. Using the Inter99 cohort, we found no difference in J-point amplitude and QTc-interval between carriers and non-carriers for 14/18 variants. There was no difference in the risk of syncope (P = 0.32), malignant ventricular arrhythmia (P = 0.96), and all-cause mortality (P = 0.59) between carriers and non-carriers. The ACMG guidelines reclassified 75% of all variants as variant-of-uncertain significance, likely benign, and benign. We identified similar to 2/3 of variants previously associated with SIDS and found no significant associations with electrocardiographic traits, syncope, malignant ventricular arrhythmia, or all-cause mortality. These data indicate that many of these variants are not highly penetrant, monogenic causes of SIDS and underline the importance of frequent reappraisal of genetic variants to avoid future misdiagnosis.

AB - We aimed to investigate the pathogenicity of cardiac ion channel variants previously associated with SIDS. We reviewed SIDS-associated variants previously reported in databases and the literature in three large population-based cohorts; The ExAC database, the Inter99 study, and the UK Biobank (UKBB). Variants were classified according to the American College of Medical Genetics and Genomics (ACMG) guidelines. Of the 92 SIDS-associated variants, 59 (64%) were present in ExAC, 18 (20%) in Inter99, and 24 (26%) in UKBB. Using the Inter99 cohort, we found no difference in J-point amplitude and QTc-interval between carriers and non-carriers for 14/18 variants. There was no difference in the risk of syncope (P = 0.32), malignant ventricular arrhythmia (P = 0.96), and all-cause mortality (P = 0.59) between carriers and non-carriers. The ACMG guidelines reclassified 75% of all variants as variant-of-uncertain significance, likely benign, and benign. We identified similar to 2/3 of variants previously associated with SIDS and found no significant associations with electrocardiographic traits, syncope, malignant ventricular arrhythmia, or all-cause mortality. These data indicate that many of these variants are not highly penetrant, monogenic causes of SIDS and underline the importance of frequent reappraisal of genetic variants to avoid future misdiagnosis.

U2 - 10.1038/s41431-019-0416-3

DO - 10.1038/s41431-019-0416-3

M3 - Journal article

C2 - 31043699

VL - 27

SP - 1427

EP - 1435

JO - European Journal of Human Genetics

JF - European Journal of Human Genetics

SN - 1018-4813

IS - 9

ER -

ID: 226789825