Several common variants modulate heart rate, PR interval and QRS duration
Hilma Holm and colleagues report genome-wide association studies to electrocardiographic measures of heart rate, PR interval, QRS duration and QT interval. Electrocardiographic measures are indicative of the function of the cardiac conduction system. To search for sequence variants that modulate hea...
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| Veröffentlicht in: | Nature genetics 2010-02, Vol.42 (2), p.117-122 |
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| creator | Holm, Hilma Gudbjartsson, Daniel F Arnar, David O Thorleifsson, Gudmar Thorgeirsson, Gudmundur Stefansdottir, Hrafnhildur Gudjonsson, Sigurjon A Jonasdottir, Aslaug Mathiesen, Ellisiv B Njølstad, Inger Nyrnes, Audhild Wilsgaard, Tom Hald, Erin M Hveem, Kristian Stoltenberg, Camilla Løchen, Maja-Lisa Kong, Augustine Thorsteinsdottir, Unnur Stefansson, Kari |
| description | Hilma Holm and colleagues report genome-wide association studies to electrocardiographic measures of heart rate, PR interval, QRS duration and QT interval.
Electrocardiographic measures are indicative of the function of the cardiac conduction system. To search for sequence variants that modulate heart rate, PR interval and QRS duration in individuals of European descent, we performed a genome-wide association study in ∼10,000 individuals and followed up the top signals in an additional ∼10,000 individuals. We identified several genome-wide significant associations (with
P
< 1.6 × 10
−7
). We identified one locus for heart rate (
MYH6
), four for PR interval (
TBX5
,
SCN10A
,
CAV1
and
ARHGAP24
) and four for QRS duration (
TBX5
,
SCN10A
, 6p21 and 10q21). We tested for association between these loci and subjects with selected arrhythmias in Icelandic and Norwegian case-control sample sets. We observed correlations between
TBX5
and
CAV1
and atrial fibrillation (
P
= 4.0 × 10
−5
and
P
= 0.00032, respectively), between
TBX5
and advanced atrioventricular block (
P
= 0.0067), and between
SCN10A
and pacemaker implantation (
P
= 0.0029). We also replicated previously described associations with the QT interval. |
| doi_str_mv | 10.1038/ng.511 |
| format | Article |
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Electrocardiographic measures are indicative of the function of the cardiac conduction system. To search for sequence variants that modulate heart rate, PR interval and QRS duration in individuals of European descent, we performed a genome-wide association study in ∼10,000 individuals and followed up the top signals in an additional ∼10,000 individuals. We identified several genome-wide significant associations (with
P
< 1.6 × 10
−7
). We identified one locus for heart rate (
MYH6
), four for PR interval (
TBX5
,
SCN10A
,
CAV1
and
ARHGAP24
) and four for QRS duration (
TBX5
,
SCN10A
, 6p21 and 10q21). We tested for association between these loci and subjects with selected arrhythmias in Icelandic and Norwegian case-control sample sets. We observed correlations between
TBX5
and
CAV1
and atrial fibrillation (
P
= 4.0 × 10
−5
and
P
= 0.00032, respectively), between
TBX5
and advanced atrioventricular block (
P
= 0.0067), and between
SCN10A
and pacemaker implantation (
P
= 0.0029). We also replicated previously described associations with the QT interval.</description><identifier>ISSN: 1061-4036</identifier><identifier>EISSN: 1546-1718</identifier><identifier>DOI: 10.1038/ng.511</identifier><identifier>PMID: 20062063</identifier><identifier>CODEN: NGENEC</identifier><language>eng</language><publisher>New York: Nature Publishing Group US</publisher><subject>631/1647/2204/1453/1448 ; 631/208/205/2138 ; 631/208/727/2000 ; 692/699/75/29 ; Aged ; Agriculture ; Animal Genetics and Genomics ; Arrhythmias, Cardiac - complications ; Arrhythmias, Cardiac - genetics ; Arrhythmias, Cardiac - physiopathology ; Atrial fibrillation ; Atrial Fibrillation - complications ; Atrial Fibrillation - genetics ; Atrial Fibrillation - physiopathology ; Atrioventricular Block - complications ; Atrioventricular Block - genetics ; Atrioventricular Block - physiopathology ; Biological and medical sciences ; Biomedical and Life Sciences ; Biomedicine ; Cancer Research ; Cardiac arrhythmia ; Cardiac Myosins - genetics ; Cardiovascular disease ; Care and treatment ; Data collection ; Diagnosis ; Electrocardiogram ; Electrocardiography ; Female ; Fundamental and applied biological sciences. Psychology ; Gene expression ; Gene Function ; Genetic aspects ; Genetic Loci - genetics ; Genetic Variation ; Genetics of eukaryotes. Biological and molecular evolution ; Genome-Wide Association Study ; Health aspects ; Heart attacks ; Heart beat ; Heart Conduction System - physiology ; Heart rate ; Heart Rate - genetics ; Human Genetics ; Humans ; Iceland ; Inheritance Patterns - genetics ; Male ; Measurement ; Middle Aged ; Mortality ; Myosin Heavy Chains - genetics ; Nitric oxide ; Pacemaker, Artificial ; Physiological aspects ; Reproducibility of Results ; Risk factors ; Sick Sinus Syndrome - complications ; Sick Sinus Syndrome - genetics ; Sick Sinus Syndrome - physiopathology ; Studies</subject><ispartof>Nature genetics, 2010-02, Vol.42 (2), p.117-122</ispartof><rights>Springer Nature America, Inc. 2010</rights><rights>2015 INIST-CNRS</rights><rights>COPYRIGHT 2010 Nature Publishing Group</rights><rights>Copyright Nature Publishing Group Feb 2010</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c599t-aa15f471ee25577911ce9638172fecd578da486ae4086cae36839355c235f4bd3</citedby><cites>FETCH-LOGICAL-c599t-aa15f471ee25577911ce9638172fecd578da486ae4086cae36839355c235f4bd3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1038/ng.511$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1038/ng.511$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>314,776,780,27901,27902,41464,42533,51294</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=22374696$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/20062063$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Holm, Hilma</creatorcontrib><creatorcontrib>Gudbjartsson, Daniel F</creatorcontrib><creatorcontrib>Arnar, David O</creatorcontrib><creatorcontrib>Thorleifsson, Gudmar</creatorcontrib><creatorcontrib>Thorgeirsson, Gudmundur</creatorcontrib><creatorcontrib>Stefansdottir, Hrafnhildur</creatorcontrib><creatorcontrib>Gudjonsson, Sigurjon A</creatorcontrib><creatorcontrib>Jonasdottir, Aslaug</creatorcontrib><creatorcontrib>Mathiesen, Ellisiv B</creatorcontrib><creatorcontrib>Njølstad, Inger</creatorcontrib><creatorcontrib>Nyrnes, Audhild</creatorcontrib><creatorcontrib>Wilsgaard, Tom</creatorcontrib><creatorcontrib>Hald, Erin M</creatorcontrib><creatorcontrib>Hveem, Kristian</creatorcontrib><creatorcontrib>Stoltenberg, Camilla</creatorcontrib><creatorcontrib>Løchen, Maja-Lisa</creatorcontrib><creatorcontrib>Kong, Augustine</creatorcontrib><creatorcontrib>Thorsteinsdottir, Unnur</creatorcontrib><creatorcontrib>Stefansson, Kari</creatorcontrib><title>Several common variants modulate heart rate, PR interval and QRS duration</title><title>Nature genetics</title><addtitle>Nat Genet</addtitle><addtitle>Nat Genet</addtitle><description>Hilma Holm and colleagues report genome-wide association studies to electrocardiographic measures of heart rate, PR interval, QRS duration and QT interval.
Electrocardiographic measures are indicative of the function of the cardiac conduction system. To search for sequence variants that modulate heart rate, PR interval and QRS duration in individuals of European descent, we performed a genome-wide association study in ∼10,000 individuals and followed up the top signals in an additional ∼10,000 individuals. We identified several genome-wide significant associations (with
P
< 1.6 × 10
−7
). We identified one locus for heart rate (
MYH6
), four for PR interval (
TBX5
,
SCN10A
,
CAV1
and
ARHGAP24
) and four for QRS duration (
TBX5
,
SCN10A
, 6p21 and 10q21). We tested for association between these loci and subjects with selected arrhythmias in Icelandic and Norwegian case-control sample sets. We observed correlations between
TBX5
and
CAV1
and atrial fibrillation (
P
= 4.0 × 10
−5
and
P
= 0.00032, respectively), between
TBX5
and advanced atrioventricular block (
P
= 0.0067), and between
SCN10A
and pacemaker implantation (
P
= 0.0029). We also replicated previously described associations with the QT interval.</description><subject>631/1647/2204/1453/1448</subject><subject>631/208/205/2138</subject><subject>631/208/727/2000</subject><subject>692/699/75/29</subject><subject>Aged</subject><subject>Agriculture</subject><subject>Animal Genetics and Genomics</subject><subject>Arrhythmias, Cardiac - complications</subject><subject>Arrhythmias, Cardiac - genetics</subject><subject>Arrhythmias, Cardiac - physiopathology</subject><subject>Atrial fibrillation</subject><subject>Atrial Fibrillation - complications</subject><subject>Atrial Fibrillation - genetics</subject><subject>Atrial Fibrillation - physiopathology</subject><subject>Atrioventricular Block - complications</subject><subject>Atrioventricular Block - genetics</subject><subject>Atrioventricular Block - physiopathology</subject><subject>Biological and medical sciences</subject><subject>Biomedical and Life Sciences</subject><subject>Biomedicine</subject><subject>Cancer Research</subject><subject>Cardiac arrhythmia</subject><subject>Cardiac Myosins - genetics</subject><subject>Cardiovascular disease</subject><subject>Care and treatment</subject><subject>Data collection</subject><subject>Diagnosis</subject><subject>Electrocardiogram</subject><subject>Electrocardiography</subject><subject>Female</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Gene expression</subject><subject>Gene Function</subject><subject>Genetic aspects</subject><subject>Genetic Loci - genetics</subject><subject>Genetic Variation</subject><subject>Genetics of eukaryotes. Biological and molecular evolution</subject><subject>Genome-Wide Association Study</subject><subject>Health aspects</subject><subject>Heart attacks</subject><subject>Heart beat</subject><subject>Heart Conduction System - physiology</subject><subject>Heart rate</subject><subject>Heart Rate - genetics</subject><subject>Human Genetics</subject><subject>Humans</subject><subject>Iceland</subject><subject>Inheritance Patterns - genetics</subject><subject>Male</subject><subject>Measurement</subject><subject>Middle Aged</subject><subject>Mortality</subject><subject>Myosin Heavy Chains - genetics</subject><subject>Nitric oxide</subject><subject>Pacemaker, Artificial</subject><subject>Physiological aspects</subject><subject>Reproducibility of Results</subject><subject>Risk factors</subject><subject>Sick Sinus Syndrome - complications</subject><subject>Sick Sinus Syndrome - genetics</subject><subject>Sick Sinus Syndrome - physiopathology</subject><subject>Studies</subject><issn>1061-4036</issn><issn>1546-1718</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2010</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>8G5</sourceid><sourceid>BENPR</sourceid><sourceid>GUQSH</sourceid><sourceid>M2O</sourceid><recordid>eNqN0m1r1TAUAOAiiptTf4IURUWw17yn_TiGLxcG03vVr-EsPa0dbbol7cX9-52x68YdIpIPCclzkpzkZNlzzhacyfJDaBea8wfZPtfKFNzy8iGNmeGFYtLsZU9SOmOMK8XKx9meYMwIZuR-tlzjBiP0uR-HYQz5BmIHYUr5MNZzDxPmvxDilEcavs-_rvIuTBg3FAChzr-t1nk901o3hqfZowb6hM-2_UH249PH70dfiuOTz8ujw-PC66qaCgCuG2U5otDa2opzj5WRJbeiQV9rW9agSgNINzUeUJpSVlJrLyTFndbyIHt7s-95HC9mTJMbuuSx7yHgOCdnpRLaai5JvvmnFGSUkorgy3vwbJxjoCycEMJoVSpB6NUNaqFH14VmnCL46x3doeClFlYyS2rxF0WtxqHzY8Cmo_mdgHc7AWQm_D21MKfkluvV_9uTn7t2m7yPY0oRG3ceuwHipePMXZeMC62jkiH4Ypv8fDpgfcv-1AiB11sAyUPfRAi-S3dOSKsMfeHtxyRaCi3Gu1e8d-QVhBPPaQ</recordid><startdate>20100201</startdate><enddate>20100201</enddate><creator>Holm, Hilma</creator><creator>Gudbjartsson, Daniel F</creator><creator>Arnar, David O</creator><creator>Thorleifsson, Gudmar</creator><creator>Thorgeirsson, Gudmundur</creator><creator>Stefansdottir, Hrafnhildur</creator><creator>Gudjonsson, Sigurjon A</creator><creator>Jonasdottir, Aslaug</creator><creator>Mathiesen, Ellisiv B</creator><creator>Njølstad, Inger</creator><creator>Nyrnes, Audhild</creator><creator>Wilsgaard, Tom</creator><creator>Hald, Erin M</creator><creator>Hveem, Kristian</creator><creator>Stoltenberg, Camilla</creator><creator>Løchen, Maja-Lisa</creator><creator>Kong, Augustine</creator><creator>Thorsteinsdottir, Unnur</creator><creator>Stefansson, Kari</creator><general>Nature Publishing Group US</general><general>Nature Publishing Group</general><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>IOV</scope><scope>ISR</scope><scope>3V.</scope><scope>7QL</scope><scope>7QP</scope><scope>7QR</scope><scope>7SS</scope><scope>7T7</scope><scope>7TK</scope><scope>7TM</scope><scope>7U9</scope><scope>7X7</scope><scope>7XB</scope><scope>88A</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>8G5</scope><scope>ABUWG</scope><scope>AEUYN</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>GUQSH</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M2O</scope><scope>M7N</scope><scope>M7P</scope><scope>MBDVC</scope><scope>P64</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>Q9U</scope><scope>RC3</scope><scope>7X8</scope></search><sort><creationdate>20100201</creationdate><title>Several common variants modulate heart rate, PR interval and QRS duration</title><author>Holm, Hilma ; 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Psychology</topic><topic>Gene expression</topic><topic>Gene Function</topic><topic>Genetic aspects</topic><topic>Genetic Loci - genetics</topic><topic>Genetic Variation</topic><topic>Genetics of eukaryotes. Biological and molecular evolution</topic><topic>Genome-Wide Association Study</topic><topic>Health aspects</topic><topic>Heart attacks</topic><topic>Heart beat</topic><topic>Heart Conduction System - physiology</topic><topic>Heart rate</topic><topic>Heart Rate - genetics</topic><topic>Human Genetics</topic><topic>Humans</topic><topic>Iceland</topic><topic>Inheritance Patterns - genetics</topic><topic>Male</topic><topic>Measurement</topic><topic>Middle Aged</topic><topic>Mortality</topic><topic>Myosin Heavy Chains - genetics</topic><topic>Nitric oxide</topic><topic>Pacemaker, Artificial</topic><topic>Physiological aspects</topic><topic>Reproducibility of Results</topic><topic>Risk factors</topic><topic>Sick Sinus Syndrome - complications</topic><topic>Sick Sinus Syndrome - genetics</topic><topic>Sick Sinus Syndrome - physiopathology</topic><topic>Studies</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Holm, 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C)</collection><collection>Biological Science Database</collection><collection>Research Library (Corporate)</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central Basic</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Nature genetics</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Holm, Hilma</au><au>Gudbjartsson, Daniel F</au><au>Arnar, David O</au><au>Thorleifsson, Gudmar</au><au>Thorgeirsson, Gudmundur</au><au>Stefansdottir, Hrafnhildur</au><au>Gudjonsson, Sigurjon A</au><au>Jonasdottir, Aslaug</au><au>Mathiesen, Ellisiv B</au><au>Njølstad, Inger</au><au>Nyrnes, Audhild</au><au>Wilsgaard, Tom</au><au>Hald, Erin M</au><au>Hveem, Kristian</au><au>Stoltenberg, Camilla</au><au>Løchen, Maja-Lisa</au><au>Kong, Augustine</au><au>Thorsteinsdottir, Unnur</au><au>Stefansson, Kari</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Several common variants modulate heart rate, PR interval and QRS duration</atitle><jtitle>Nature genetics</jtitle><stitle>Nat Genet</stitle><addtitle>Nat Genet</addtitle><date>2010-02-01</date><risdate>2010</risdate><volume>42</volume><issue>2</issue><spage>117</spage><epage>122</epage><pages>117-122</pages><issn>1061-4036</issn><eissn>1546-1718</eissn><coden>NGENEC</coden><abstract>Hilma Holm and colleagues report genome-wide association studies to electrocardiographic measures of heart rate, PR interval, QRS duration and QT interval.
Electrocardiographic measures are indicative of the function of the cardiac conduction system. To search for sequence variants that modulate heart rate, PR interval and QRS duration in individuals of European descent, we performed a genome-wide association study in ∼10,000 individuals and followed up the top signals in an additional ∼10,000 individuals. We identified several genome-wide significant associations (with
P
< 1.6 × 10
−7
). We identified one locus for heart rate (
MYH6
), four for PR interval (
TBX5
,
SCN10A
,
CAV1
and
ARHGAP24
) and four for QRS duration (
TBX5
,
SCN10A
, 6p21 and 10q21). We tested for association between these loci and subjects with selected arrhythmias in Icelandic and Norwegian case-control sample sets. We observed correlations between
TBX5
and
CAV1
and atrial fibrillation (
P
= 4.0 × 10
−5
and
P
= 0.00032, respectively), between
TBX5
and advanced atrioventricular block (
P
= 0.0067), and between
SCN10A
and pacemaker implantation (
P
= 0.0029). We also replicated previously described associations with the QT interval.</abstract><cop>New York</cop><pub>Nature Publishing Group US</pub><pmid>20062063</pmid><doi>10.1038/ng.511</doi><tpages>6</tpages></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1061-4036 |
| ispartof | Nature genetics, 2010-02, Vol.42 (2), p.117-122 |
| issn | 1061-4036 1546-1718 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_734257513 |
| source | MEDLINE; Springer Nature - Complete Springer Journals; Nature Journals Online |
| subjects | 631/1647/2204/1453/1448 631/208/205/2138 631/208/727/2000 692/699/75/29 Aged Agriculture Animal Genetics and Genomics Arrhythmias, Cardiac - complications Arrhythmias, Cardiac - genetics Arrhythmias, Cardiac - physiopathology Atrial fibrillation Atrial Fibrillation - complications Atrial Fibrillation - genetics Atrial Fibrillation - physiopathology Atrioventricular Block - complications Atrioventricular Block - genetics Atrioventricular Block - physiopathology Biological and medical sciences Biomedical and Life Sciences Biomedicine Cancer Research Cardiac arrhythmia Cardiac Myosins - genetics Cardiovascular disease Care and treatment Data collection Diagnosis Electrocardiogram Electrocardiography Female Fundamental and applied biological sciences. Psychology Gene expression Gene Function Genetic aspects Genetic Loci - genetics Genetic Variation Genetics of eukaryotes. Biological and molecular evolution Genome-Wide Association Study Health aspects Heart attacks Heart beat Heart Conduction System - physiology Heart rate Heart Rate - genetics Human Genetics Humans Iceland Inheritance Patterns - genetics Male Measurement Middle Aged Mortality Myosin Heavy Chains - genetics Nitric oxide Pacemaker, Artificial Physiological aspects Reproducibility of Results Risk factors Sick Sinus Syndrome - complications Sick Sinus Syndrome - genetics Sick Sinus Syndrome - physiopathology Studies |
| title | Several common variants modulate heart rate, PR interval and QRS duration |
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