Genetic insight into sick sinus syndrome
Abstract Aims The aim of this study was to use human genetics to investigate the pathogenesis of sick sinus syndrome (SSS) and the role of risk factors in its development. Methods and results We performed a genome-wide association study of 6469 SSS cases and 1 000 187 controls from deCODE genetics,...
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| Veröffentlicht in: | European heart journal 2021-05, Vol.42 (20), p.1959-1971 |
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| container_end_page | 1971 |
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| container_start_page | 1959 |
| container_title | European heart journal |
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| creator | Thorolfsdottir, Rosa B Sveinbjornsson, Gardar Aegisdottir, Hildur M Benonisdottir, Stefania Stefansdottir, Lilja Ivarsdottir, Erna V Halldorsson, Gisli H Sigurdsson, Jon K Torp-Pedersen, Christian Weeke, Peter E Brunak, Søren Westergaard, David Pedersen, Ole B Sorensen, Erik Nielsen, Kaspar R Burgdorf, Kristoffer S Banasik, Karina Brumpton, Ben Zhou, Wei Oddsson, Asmundur Tragante, Vinicius Hjorleifsson, Kristjan E Davidsson, Olafur B Rajamani, Sridharan Jonsson, Stefan Torfason, Bjarni Valgardsson, Atli S Thorgeirsson, Gudmundur Frigge, Michael L Thorleifsson, Gudmar Norddahl, Gudmundur L Helgadottir, Anna Gretarsdottir, Solveig Sulem, Patrick Jonsdottir, Ingileif Willer, Cristen J Hveem, Kristian Bundgaard, Henning Ullum, Henrik Arnar, David O Thorsteinsdottir, Unnur Gudbjartsson, Daniel F Holm, Hilma Stefansson, Kari |
| description | Abstract
Aims
The aim of this study was to use human genetics to investigate the pathogenesis of sick sinus syndrome (SSS) and the role of risk factors in its development.
Methods and results
We performed a genome-wide association study of 6469 SSS cases and 1 000 187 controls from deCODE genetics, the Copenhagen Hospital Biobank, UK Biobank, and the HUNT study. Variants at six loci associated with SSS, a reported missense variant in MYH6, known atrial fibrillation (AF)/electrocardiogram variants at PITX2, ZFHX3, TTN/CCDC141, and SCN10A and a low-frequency (MAF = 1.1–1.8%) missense variant, p.Gly62Cys in KRT8 encoding the intermediate filament protein keratin 8. A full genotypic model best described the p.Gly62Cys association (P = 1.6 × 10−20), with an odds ratio (OR) of 1.44 for heterozygotes and a disproportionally large OR of 13.99 for homozygotes. All the SSS variants increased the risk of pacemaker implantation. Their association with AF varied and p.Gly62Cys was the only variant not associating with any other arrhythmia or cardiovascular disease. We tested 17 exposure phenotypes in polygenic score (PGS) and Mendelian randomization analyses. Only two associated with the risk of SSS in Mendelian randomization, AF, and lower heart rate, suggesting causality. Powerful PGS analyses provided convincing evidence against causal associations for body mass index, cholesterol, triglycerides, and type 2 diabetes (P > 0.05).
Conclusion
We report the associations of variants at six loci with SSS, including a missense variant in KRT8 that confers high risk in homozygotes and points to a mechanism specific to SSS development. Mendelian randomization supports a causal role for AF in the development of SSS.
Graphical Abstract
Summary of genetic insight into the pathogenesis of SSS and the role of risk factors in its development. Variants at six loci (named by corresponding gene names) were identified through GWAS and their unique phenotypic associations provide insight into distinct pathways underlying SSS. Investigation of the role of risk factors in SSS development supported a causal role for AF and heart rate and provided convincing evidence against causality for BMI, cholesterol (HDL and non-HDL), triglycerides and T2D. Mendelian randomization did not support causality for CAD, ischaemic stroke, heart failure, PR interval or QRS duration (not shown in figure). Red and blue arrows represent positive and negative associations, respectively. |
| doi_str_mv | 10.1093/eurheartj/ehaa1108 |
| format | Article |
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Aims
The aim of this study was to use human genetics to investigate the pathogenesis of sick sinus syndrome (SSS) and the role of risk factors in its development.
Methods and results
We performed a genome-wide association study of 6469 SSS cases and 1 000 187 controls from deCODE genetics, the Copenhagen Hospital Biobank, UK Biobank, and the HUNT study. Variants at six loci associated with SSS, a reported missense variant in MYH6, known atrial fibrillation (AF)/electrocardiogram variants at PITX2, ZFHX3, TTN/CCDC141, and SCN10A and a low-frequency (MAF = 1.1–1.8%) missense variant, p.Gly62Cys in KRT8 encoding the intermediate filament protein keratin 8. A full genotypic model best described the p.Gly62Cys association (P = 1.6 × 10−20), with an odds ratio (OR) of 1.44 for heterozygotes and a disproportionally large OR of 13.99 for homozygotes. All the SSS variants increased the risk of pacemaker implantation. Their association with AF varied and p.Gly62Cys was the only variant not associating with any other arrhythmia or cardiovascular disease. We tested 17 exposure phenotypes in polygenic score (PGS) and Mendelian randomization analyses. Only two associated with the risk of SSS in Mendelian randomization, AF, and lower heart rate, suggesting causality. Powerful PGS analyses provided convincing evidence against causal associations for body mass index, cholesterol, triglycerides, and type 2 diabetes (P > 0.05).
Conclusion
We report the associations of variants at six loci with SSS, including a missense variant in KRT8 that confers high risk in homozygotes and points to a mechanism specific to SSS development. Mendelian randomization supports a causal role for AF in the development of SSS.
Graphical Abstract
Summary of genetic insight into the pathogenesis of SSS and the role of risk factors in its development. Variants at six loci (named by corresponding gene names) were identified through GWAS and their unique phenotypic associations provide insight into distinct pathways underlying SSS. Investigation of the role of risk factors in SSS development supported a causal role for AF and heart rate and provided convincing evidence against causality for BMI, cholesterol (HDL and non-HDL), triglycerides and T2D. Mendelian randomization did not support causality for CAD, ischaemic stroke, heart failure, PR interval or QRS duration (not shown in figure). Red and blue arrows represent positive and negative associations, respectively.</description><identifier>ISSN: 0195-668X</identifier><identifier>EISSN: 1522-9645</identifier><identifier>DOI: 10.1093/eurheartj/ehaa1108</identifier><identifier>PMID: 33580673</identifier><language>eng</language><publisher>England: Oxford University Press</publisher><subject>Clinical Research</subject><ispartof>European heart journal, 2021-05, Vol.42 (20), p.1959-1971</ispartof><rights>The Author(s) 2021. Published by Oxford University Press on behalf of the European Society of Cardiology. 2021</rights><rights>The Author(s) 2021. Published by Oxford University Press on behalf of the European Society of Cardiology.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c473t-c372ea8f011cf1caa04b36a65b59904bc5230012f9d533d059d181785d7a94663</citedby><cites>FETCH-LOGICAL-c473t-c372ea8f011cf1caa04b36a65b59904bc5230012f9d533d059d181785d7a94663</cites><orcidid>0000-0003-4406-9643 ; 0000-0003-1676-864X ; 0000-0001-7067-9862 ; 0000-0001-7475-0398 ; 0000-0002-3058-1059 ; 0000-0001-8339-150X ; 0000-0002-8223-8957 ; 0000-0003-2892-6131 ; 0000-0001-7719-0859 ; 0000-0003-0128-8432 ; 0000-0002-9517-6636 ; 0000-0002-2069-0681 ; 0000-0001-5814-6844 ; 0000-0002-7049-2827 ; 0000-0002-4606-5163 ; 0000-0003-2429-9468 ; 0000-0001-5019-514X ; 0000-0002-7851-1818 ; 0000-0001-7123-6123 ; 0000-0002-5222-9857 ; 0000-0003-4623-9087 ; 0000-0003-2312-5976 ; 0000-0001-7306-9058 ; 0000-0003-2489-2499 ; 0000-0001-5645-4966</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,780,784,885,1584,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/33580673$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Thorolfsdottir, Rosa B</creatorcontrib><creatorcontrib>Sveinbjornsson, Gardar</creatorcontrib><creatorcontrib>Aegisdottir, Hildur M</creatorcontrib><creatorcontrib>Benonisdottir, Stefania</creatorcontrib><creatorcontrib>Stefansdottir, Lilja</creatorcontrib><creatorcontrib>Ivarsdottir, Erna V</creatorcontrib><creatorcontrib>Halldorsson, Gisli H</creatorcontrib><creatorcontrib>Sigurdsson, Jon K</creatorcontrib><creatorcontrib>Torp-Pedersen, Christian</creatorcontrib><creatorcontrib>Weeke, Peter E</creatorcontrib><creatorcontrib>Brunak, Søren</creatorcontrib><creatorcontrib>Westergaard, David</creatorcontrib><creatorcontrib>Pedersen, Ole B</creatorcontrib><creatorcontrib>Sorensen, Erik</creatorcontrib><creatorcontrib>Nielsen, Kaspar R</creatorcontrib><creatorcontrib>Burgdorf, Kristoffer S</creatorcontrib><creatorcontrib>Banasik, Karina</creatorcontrib><creatorcontrib>Brumpton, Ben</creatorcontrib><creatorcontrib>Zhou, Wei</creatorcontrib><creatorcontrib>Oddsson, Asmundur</creatorcontrib><creatorcontrib>Tragante, Vinicius</creatorcontrib><creatorcontrib>Hjorleifsson, Kristjan E</creatorcontrib><creatorcontrib>Davidsson, Olafur B</creatorcontrib><creatorcontrib>Rajamani, Sridharan</creatorcontrib><creatorcontrib>Jonsson, Stefan</creatorcontrib><creatorcontrib>Torfason, Bjarni</creatorcontrib><creatorcontrib>Valgardsson, Atli S</creatorcontrib><creatorcontrib>Thorgeirsson, Gudmundur</creatorcontrib><creatorcontrib>Frigge, Michael L</creatorcontrib><creatorcontrib>Thorleifsson, Gudmar</creatorcontrib><creatorcontrib>Norddahl, Gudmundur L</creatorcontrib><creatorcontrib>Helgadottir, Anna</creatorcontrib><creatorcontrib>Gretarsdottir, Solveig</creatorcontrib><creatorcontrib>Sulem, Patrick</creatorcontrib><creatorcontrib>Jonsdottir, Ingileif</creatorcontrib><creatorcontrib>Willer, Cristen J</creatorcontrib><creatorcontrib>Hveem, Kristian</creatorcontrib><creatorcontrib>Bundgaard, Henning</creatorcontrib><creatorcontrib>Ullum, Henrik</creatorcontrib><creatorcontrib>Arnar, David O</creatorcontrib><creatorcontrib>Thorsteinsdottir, Unnur</creatorcontrib><creatorcontrib>Gudbjartsson, Daniel F</creatorcontrib><creatorcontrib>Holm, Hilma</creatorcontrib><creatorcontrib>Stefansson, Kari</creatorcontrib><creatorcontrib>DBDS Genomic Consortium</creatorcontrib><creatorcontrib>DBDS Genomic Consortium</creatorcontrib><title>Genetic insight into sick sinus syndrome</title><title>European heart journal</title><addtitle>Eur Heart J</addtitle><description>Abstract
Aims
The aim of this study was to use human genetics to investigate the pathogenesis of sick sinus syndrome (SSS) and the role of risk factors in its development.
Methods and results
We performed a genome-wide association study of 6469 SSS cases and 1 000 187 controls from deCODE genetics, the Copenhagen Hospital Biobank, UK Biobank, and the HUNT study. Variants at six loci associated with SSS, a reported missense variant in MYH6, known atrial fibrillation (AF)/electrocardiogram variants at PITX2, ZFHX3, TTN/CCDC141, and SCN10A and a low-frequency (MAF = 1.1–1.8%) missense variant, p.Gly62Cys in KRT8 encoding the intermediate filament protein keratin 8. A full genotypic model best described the p.Gly62Cys association (P = 1.6 × 10−20), with an odds ratio (OR) of 1.44 for heterozygotes and a disproportionally large OR of 13.99 for homozygotes. All the SSS variants increased the risk of pacemaker implantation. Their association with AF varied and p.Gly62Cys was the only variant not associating with any other arrhythmia or cardiovascular disease. We tested 17 exposure phenotypes in polygenic score (PGS) and Mendelian randomization analyses. Only two associated with the risk of SSS in Mendelian randomization, AF, and lower heart rate, suggesting causality. Powerful PGS analyses provided convincing evidence against causal associations for body mass index, cholesterol, triglycerides, and type 2 diabetes (P > 0.05).
Conclusion
We report the associations of variants at six loci with SSS, including a missense variant in KRT8 that confers high risk in homozygotes and points to a mechanism specific to SSS development. Mendelian randomization supports a causal role for AF in the development of SSS.
Graphical Abstract
Summary of genetic insight into the pathogenesis of SSS and the role of risk factors in its development. Variants at six loci (named by corresponding gene names) were identified through GWAS and their unique phenotypic associations provide insight into distinct pathways underlying SSS. Investigation of the role of risk factors in SSS development supported a causal role for AF and heart rate and provided convincing evidence against causality for BMI, cholesterol (HDL and non-HDL), triglycerides and T2D. Mendelian randomization did not support causality for CAD, ischaemic stroke, heart failure, PR interval or QRS duration (not shown in figure). 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insight into sick sinus syndrome</title><author>Thorolfsdottir, Rosa B ; Sveinbjornsson, Gardar ; Aegisdottir, Hildur M ; Benonisdottir, Stefania ; Stefansdottir, Lilja ; Ivarsdottir, Erna V ; Halldorsson, Gisli H ; Sigurdsson, Jon K ; Torp-Pedersen, Christian ; Weeke, Peter E ; Brunak, Søren ; Westergaard, David ; Pedersen, Ole B ; Sorensen, Erik ; Nielsen, Kaspar R ; Burgdorf, Kristoffer S ; Banasik, Karina ; Brumpton, Ben ; Zhou, Wei ; Oddsson, Asmundur ; Tragante, Vinicius ; Hjorleifsson, Kristjan E ; Davidsson, Olafur B ; Rajamani, Sridharan ; Jonsson, Stefan ; Torfason, Bjarni ; Valgardsson, Atli S ; Thorgeirsson, Gudmundur ; Frigge, Michael L ; Thorleifsson, Gudmar ; Norddahl, Gudmundur L ; Helgadottir, Anna ; Gretarsdottir, Solveig ; Sulem, Patrick ; Jonsdottir, Ingileif ; Willer, Cristen J ; Hveem, Kristian ; Bundgaard, Henning ; Ullum, Henrik ; Arnar, David O ; Thorsteinsdottir, Unnur ; Gudbjartsson, Daniel F ; Holm, Hilma ; Stefansson, Kari</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c473t-c372ea8f011cf1caa04b36a65b59904bc5230012f9d533d059d181785d7a94663</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2021</creationdate><topic>Clinical Research</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Thorolfsdottir, Rosa B</creatorcontrib><creatorcontrib>Sveinbjornsson, Gardar</creatorcontrib><creatorcontrib>Aegisdottir, Hildur M</creatorcontrib><creatorcontrib>Benonisdottir, Stefania</creatorcontrib><creatorcontrib>Stefansdottir, Lilja</creatorcontrib><creatorcontrib>Ivarsdottir, Erna V</creatorcontrib><creatorcontrib>Halldorsson, Gisli H</creatorcontrib><creatorcontrib>Sigurdsson, Jon K</creatorcontrib><creatorcontrib>Torp-Pedersen, Christian</creatorcontrib><creatorcontrib>Weeke, Peter E</creatorcontrib><creatorcontrib>Brunak, Søren</creatorcontrib><creatorcontrib>Westergaard, David</creatorcontrib><creatorcontrib>Pedersen, Ole B</creatorcontrib><creatorcontrib>Sorensen, Erik</creatorcontrib><creatorcontrib>Nielsen, Kaspar R</creatorcontrib><creatorcontrib>Burgdorf, Kristoffer S</creatorcontrib><creatorcontrib>Banasik, Karina</creatorcontrib><creatorcontrib>Brumpton, Ben</creatorcontrib><creatorcontrib>Zhou, Wei</creatorcontrib><creatorcontrib>Oddsson, Asmundur</creatorcontrib><creatorcontrib>Tragante, Vinicius</creatorcontrib><creatorcontrib>Hjorleifsson, Kristjan E</creatorcontrib><creatorcontrib>Davidsson, Olafur B</creatorcontrib><creatorcontrib>Rajamani, Sridharan</creatorcontrib><creatorcontrib>Jonsson, Stefan</creatorcontrib><creatorcontrib>Torfason, Bjarni</creatorcontrib><creatorcontrib>Valgardsson, Atli S</creatorcontrib><creatorcontrib>Thorgeirsson, Gudmundur</creatorcontrib><creatorcontrib>Frigge, Michael L</creatorcontrib><creatorcontrib>Thorleifsson, Gudmar</creatorcontrib><creatorcontrib>Norddahl, Gudmundur L</creatorcontrib><creatorcontrib>Helgadottir, Anna</creatorcontrib><creatorcontrib>Gretarsdottir, Solveig</creatorcontrib><creatorcontrib>Sulem, Patrick</creatorcontrib><creatorcontrib>Jonsdottir, Ingileif</creatorcontrib><creatorcontrib>Willer, Cristen J</creatorcontrib><creatorcontrib>Hveem, Kristian</creatorcontrib><creatorcontrib>Bundgaard, Henning</creatorcontrib><creatorcontrib>Ullum, Henrik</creatorcontrib><creatorcontrib>Arnar, David O</creatorcontrib><creatorcontrib>Thorsteinsdottir, Unnur</creatorcontrib><creatorcontrib>Gudbjartsson, Daniel F</creatorcontrib><creatorcontrib>Holm, Hilma</creatorcontrib><creatorcontrib>Stefansson, Kari</creatorcontrib><creatorcontrib>DBDS Genomic Consortium</creatorcontrib><creatorcontrib>DBDS Genomic Consortium</creatorcontrib><collection>Access via Oxford University Press (Open Access Collection)</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>European heart journal</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Thorolfsdottir, Rosa B</au><au>Sveinbjornsson, Gardar</au><au>Aegisdottir, Hildur M</au><au>Benonisdottir, Stefania</au><au>Stefansdottir, Lilja</au><au>Ivarsdottir, Erna V</au><au>Halldorsson, Gisli H</au><au>Sigurdsson, Jon K</au><au>Torp-Pedersen, Christian</au><au>Weeke, Peter E</au><au>Brunak, Søren</au><au>Westergaard, David</au><au>Pedersen, Ole B</au><au>Sorensen, Erik</au><au>Nielsen, Kaspar R</au><au>Burgdorf, Kristoffer S</au><au>Banasik, Karina</au><au>Brumpton, Ben</au><au>Zhou, Wei</au><au>Oddsson, Asmundur</au><au>Tragante, Vinicius</au><au>Hjorleifsson, Kristjan E</au><au>Davidsson, Olafur B</au><au>Rajamani, Sridharan</au><au>Jonsson, Stefan</au><au>Torfason, Bjarni</au><au>Valgardsson, Atli S</au><au>Thorgeirsson, Gudmundur</au><au>Frigge, Michael L</au><au>Thorleifsson, Gudmar</au><au>Norddahl, Gudmundur L</au><au>Helgadottir, Anna</au><au>Gretarsdottir, Solveig</au><au>Sulem, Patrick</au><au>Jonsdottir, Ingileif</au><au>Willer, Cristen J</au><au>Hveem, Kristian</au><au>Bundgaard, Henning</au><au>Ullum, Henrik</au><au>Arnar, David O</au><au>Thorsteinsdottir, Unnur</au><au>Gudbjartsson, Daniel F</au><au>Holm, Hilma</au><au>Stefansson, Kari</au><aucorp>DBDS Genomic Consortium</aucorp><aucorp>DBDS Genomic Consortium</aucorp><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Genetic insight into sick sinus syndrome</atitle><jtitle>European heart journal</jtitle><addtitle>Eur Heart J</addtitle><date>2021-05-21</date><risdate>2021</risdate><volume>42</volume><issue>20</issue><spage>1959</spage><epage>1971</epage><pages>1959-1971</pages><issn>0195-668X</issn><eissn>1522-9645</eissn><abstract>Abstract
Aims
The aim of this study was to use human genetics to investigate the pathogenesis of sick sinus syndrome (SSS) and the role of risk factors in its development.
Methods and results
We performed a genome-wide association study of 6469 SSS cases and 1 000 187 controls from deCODE genetics, the Copenhagen Hospital Biobank, UK Biobank, and the HUNT study. Variants at six loci associated with SSS, a reported missense variant in MYH6, known atrial fibrillation (AF)/electrocardiogram variants at PITX2, ZFHX3, TTN/CCDC141, and SCN10A and a low-frequency (MAF = 1.1–1.8%) missense variant, p.Gly62Cys in KRT8 encoding the intermediate filament protein keratin 8. A full genotypic model best described the p.Gly62Cys association (P = 1.6 × 10−20), with an odds ratio (OR) of 1.44 for heterozygotes and a disproportionally large OR of 13.99 for homozygotes. All the SSS variants increased the risk of pacemaker implantation. Their association with AF varied and p.Gly62Cys was the only variant not associating with any other arrhythmia or cardiovascular disease. We tested 17 exposure phenotypes in polygenic score (PGS) and Mendelian randomization analyses. Only two associated with the risk of SSS in Mendelian randomization, AF, and lower heart rate, suggesting causality. Powerful PGS analyses provided convincing evidence against causal associations for body mass index, cholesterol, triglycerides, and type 2 diabetes (P > 0.05).
Conclusion
We report the associations of variants at six loci with SSS, including a missense variant in KRT8 that confers high risk in homozygotes and points to a mechanism specific to SSS development. Mendelian randomization supports a causal role for AF in the development of SSS.
Graphical Abstract
Summary of genetic insight into the pathogenesis of SSS and the role of risk factors in its development. Variants at six loci (named by corresponding gene names) were identified through GWAS and their unique phenotypic associations provide insight into distinct pathways underlying SSS. Investigation of the role of risk factors in SSS development supported a causal role for AF and heart rate and provided convincing evidence against causality for BMI, cholesterol (HDL and non-HDL), triglycerides and T2D. Mendelian randomization did not support causality for CAD, ischaemic stroke, heart failure, PR interval or QRS duration (not shown in figure). Red and blue arrows represent positive and negative associations, respectively.</abstract><cop>England</cop><pub>Oxford University Press</pub><pmid>33580673</pmid><doi>10.1093/eurheartj/ehaa1108</doi><tpages>13</tpages><orcidid>https://orcid.org/0000-0003-4406-9643</orcidid><orcidid>https://orcid.org/0000-0003-1676-864X</orcidid><orcidid>https://orcid.org/0000-0001-7067-9862</orcidid><orcidid>https://orcid.org/0000-0001-7475-0398</orcidid><orcidid>https://orcid.org/0000-0002-3058-1059</orcidid><orcidid>https://orcid.org/0000-0001-8339-150X</orcidid><orcidid>https://orcid.org/0000-0002-8223-8957</orcidid><orcidid>https://orcid.org/0000-0003-2892-6131</orcidid><orcidid>https://orcid.org/0000-0001-7719-0859</orcidid><orcidid>https://orcid.org/0000-0003-0128-8432</orcidid><orcidid>https://orcid.org/0000-0002-9517-6636</orcidid><orcidid>https://orcid.org/0000-0002-2069-0681</orcidid><orcidid>https://orcid.org/0000-0001-5814-6844</orcidid><orcidid>https://orcid.org/0000-0002-7049-2827</orcidid><orcidid>https://orcid.org/0000-0002-4606-5163</orcidid><orcidid>https://orcid.org/0000-0003-2429-9468</orcidid><orcidid>https://orcid.org/0000-0001-5019-514X</orcidid><orcidid>https://orcid.org/0000-0002-7851-1818</orcidid><orcidid>https://orcid.org/0000-0001-7123-6123</orcidid><orcidid>https://orcid.org/0000-0002-5222-9857</orcidid><orcidid>https://orcid.org/0000-0003-4623-9087</orcidid><orcidid>https://orcid.org/0000-0003-2312-5976</orcidid><orcidid>https://orcid.org/0000-0001-7306-9058</orcidid><orcidid>https://orcid.org/0000-0003-2489-2499</orcidid><orcidid>https://orcid.org/0000-0001-5645-4966</orcidid><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0195-668X |
| ispartof | European heart journal, 2021-05, Vol.42 (20), p.1959-1971 |
| issn | 0195-668X 1522-9645 |
| language | eng |
| recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_8140484 |
| source | Oxford University Press Journals All Titles (1996-Current); EZB-FREE-00999 freely available EZB journals; Alma/SFX Local Collection |
| subjects | Clinical Research |
| title | Genetic insight into sick sinus syndrome |
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