Common genetic variation near the phospholamban gene is associated with cardiac repolarisation: meta-analysis of three genome-wide association studies.
To identify loci affecting the electrocardiographic QT interval, a measure of cardiac repolarisation associated with risk of ventricular arrhythmias and sudden cardiac death, we conducted a meta-analysis of three genome-wide association studies (GWAS) including 3,558 subjects from the TwinsUK and BR...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
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| Format: | Journal article |
| Language: | English |
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2009
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| _version_ | 1797104573818601472 |
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| author | Nolte, I Wallace, C Newhouse, S Waggott, D Fu, J Soranzo, N Gwilliam, R Deloukas, P Savelieva, I Zheng, D Dalageorgou, C Farrall, M Samani, N Connell, J Brown, M Dominiczak, A Lathrop, M Zeggini, E Wain, L Newton-Cheh, C Eijgelsheim, M Rice, K de Bakker, P Pfeufer, A Sanna, S Arking, D Asselbergs, F Spector, T Carter, N Jeffery, S Tobin, M Caulfield, M Snieder, H Paterson, A Munroe, P Jamshidi, Y |
| author_facet | Nolte, I Wallace, C Newhouse, S Waggott, D Fu, J Soranzo, N Gwilliam, R Deloukas, P Savelieva, I Zheng, D Dalageorgou, C Farrall, M Samani, N Connell, J Brown, M Dominiczak, A Lathrop, M Zeggini, E Wain, L Newton-Cheh, C Eijgelsheim, M Rice, K de Bakker, P Pfeufer, A Sanna, S Arking, D Asselbergs, F Spector, T Carter, N Jeffery, S Tobin, M Caulfield, M Snieder, H Paterson, A Munroe, P Jamshidi, Y |
| author_sort | Nolte, I |
| collection | OXFORD |
| description | To identify loci affecting the electrocardiographic QT interval, a measure of cardiac repolarisation associated with risk of ventricular arrhythmias and sudden cardiac death, we conducted a meta-analysis of three genome-wide association studies (GWAS) including 3,558 subjects from the TwinsUK and BRIGHT cohorts in the UK and the DCCT/EDIC cohort from North America. Five loci were significantly associated with QT interval at P<1x10(-6). To validate these findings we performed an in silico comparison with data from two QT consortia: QTSCD (n = 15,842) and QTGEN (n = 13,685). Analysis confirmed the association between common variants near NOS1AP (P = 1.4x10(-83)) and the phospholamban (PLN) gene (P = 1.9x10(-29)). The most associated SNP near NOS1AP (rs12143842) explains 0.82% variance; the SNP near PLN (rs11153730) explains 0.74% variance of QT interval duration. We found no evidence for interaction between these two SNPs (P = 0.99). PLN is a key regulator of cardiac diastolic function and is involved in regulating intracellular calcium cycling, it has only recently been identified as a susceptibility locus for QT interval. These data offer further mechanistic insights into genetic influence on the QT interval which may predispose to life threatening arrhythmias and sudden cardiac death. |
| first_indexed | 2024-03-07T06:35:39Z |
| format | Journal article |
| id | oxford-uuid:f78a5f9b-1e1f-4419-8f8c-791be13b926c |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T06:35:39Z |
| publishDate | 2009 |
| record_format | dspace |
| spelling | oxford-uuid:f78a5f9b-1e1f-4419-8f8c-791be13b926c2022-03-27T12:43:34ZCommon genetic variation near the phospholamban gene is associated with cardiac repolarisation: meta-analysis of three genome-wide association studies.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:f78a5f9b-1e1f-4419-8f8c-791be13b926cEnglishSymplectic Elements at Oxford2009Nolte, IWallace, CNewhouse, SWaggott, DFu, JSoranzo, NGwilliam, RDeloukas, PSavelieva, IZheng, DDalageorgou, CFarrall, MSamani, NConnell, JBrown, MDominiczak, ALathrop, MZeggini, EWain, LNewton-Cheh, CEijgelsheim, MRice, Kde Bakker, PPfeufer, ASanna, SArking, DAsselbergs, FSpector, TCarter, NJeffery, STobin, MCaulfield, MSnieder, HPaterson, AMunroe, PJamshidi, YTo identify loci affecting the electrocardiographic QT interval, a measure of cardiac repolarisation associated with risk of ventricular arrhythmias and sudden cardiac death, we conducted a meta-analysis of three genome-wide association studies (GWAS) including 3,558 subjects from the TwinsUK and BRIGHT cohorts in the UK and the DCCT/EDIC cohort from North America. Five loci were significantly associated with QT interval at P<1x10(-6). To validate these findings we performed an in silico comparison with data from two QT consortia: QTSCD (n = 15,842) and QTGEN (n = 13,685). Analysis confirmed the association between common variants near NOS1AP (P = 1.4x10(-83)) and the phospholamban (PLN) gene (P = 1.9x10(-29)). The most associated SNP near NOS1AP (rs12143842) explains 0.82% variance; the SNP near PLN (rs11153730) explains 0.74% variance of QT interval duration. We found no evidence for interaction between these two SNPs (P = 0.99). PLN is a key regulator of cardiac diastolic function and is involved in regulating intracellular calcium cycling, it has only recently been identified as a susceptibility locus for QT interval. These data offer further mechanistic insights into genetic influence on the QT interval which may predispose to life threatening arrhythmias and sudden cardiac death. |
| spellingShingle | Nolte, I Wallace, C Newhouse, S Waggott, D Fu, J Soranzo, N Gwilliam, R Deloukas, P Savelieva, I Zheng, D Dalageorgou, C Farrall, M Samani, N Connell, J Brown, M Dominiczak, A Lathrop, M Zeggini, E Wain, L Newton-Cheh, C Eijgelsheim, M Rice, K de Bakker, P Pfeufer, A Sanna, S Arking, D Asselbergs, F Spector, T Carter, N Jeffery, S Tobin, M Caulfield, M Snieder, H Paterson, A Munroe, P Jamshidi, Y Common genetic variation near the phospholamban gene is associated with cardiac repolarisation: meta-analysis of three genome-wide association studies. |
| title | Common genetic variation near the phospholamban gene is associated with cardiac repolarisation: meta-analysis of three genome-wide association studies. |
| title_full | Common genetic variation near the phospholamban gene is associated with cardiac repolarisation: meta-analysis of three genome-wide association studies. |
| title_fullStr | Common genetic variation near the phospholamban gene is associated with cardiac repolarisation: meta-analysis of three genome-wide association studies. |
| title_full_unstemmed | Common genetic variation near the phospholamban gene is associated with cardiac repolarisation: meta-analysis of three genome-wide association studies. |
| title_short | Common genetic variation near the phospholamban gene is associated with cardiac repolarisation: meta-analysis of three genome-wide association studies. |
| title_sort | common genetic variation near the phospholamban gene is associated with cardiac repolarisation meta analysis of three genome wide association studies |
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