在3个欧洲遗传隔离人群中对RR间期和QT间期持续时间进行全基因组关联扫描：EUROSPAN项目。
A genome-wide association scan of RR and QT interval duration in 3 European genetically isolated populations: the EUROSPAN project.
作者信息
Marroni Fabio, Pfeufer Arne, Aulchenko Yurii S, Franklin Christopher S, Isaacs Aaron, Pichler Irene, Wild Sarah H, Oostra Ben A, Wright Alan F, Campbell Harry, Witteman Jacqueline C, Kääb Stefan, Hicks Andrew A, Gyllensten Ulf, Rudan Igor, Meitinger Thomas, Pattaro Cristian, van Duijn Cornelia M, Wilson James F, Pramstaller Peter P
机构信息
Institute of Genetic Medicine, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Munich, Germany.
出版信息
Circ Cardiovasc Genet. 2009 Aug;2(4):322-8. doi: 10.1161/CIRCGENETICS.108.833806. Epub 2009 May 15.
Abstract
BACKGROUND
We set out to identify common genetic determinants of the length of the RR and QT intervals in 2325 individuals from isolated European populations.
METHODS AND RESULTS
We analyzed the heart rate at rest, measured as the RR interval, and the length of the corrected QT interval for association with 318 237 single-nucleotide polymorphisms. The RR interval was associated with common variants within GPR133, a G-protein-coupled receptor (rs885389, P=3.9 x 10(-8)). The QT interval was associated with the earlier reported NOS1AP gene (rs2880058, P=2.00 x 10(-10)) and with a region on chromosome 13 (rs2478333, P=4.34 x 10(-8)), which is 100 kb from the closest known transcript LOC730174 and has previously not been associated with the length of the QT interval.
CONCLUSIONS
Our results suggested an association between the RR interval and GPR133 and confirmed an association between the QT interval and NOS1AP.
摘要
背景
我们着手在来自孤立欧洲人群的2325名个体中确定RR间期和QT间期长度的常见遗传决定因素。
方法与结果
我们分析了静息心率（以RR间期衡量）以及校正QT间期的长度与318237个单核苷酸多态性的关联。RR间期与G蛋白偶联受体GPR133内的常见变异相关（rs885389，P = 3.9×10⁻⁸）。QT间期与先前报道的NOS1AP基因（rs2880058，P = 2.00×10⁻¹⁰）以及13号染色体上的一个区域（rs2478333，P = 4.34×10⁻⁸）相关，该区域距离最近已知的转录本LOC730174有100 kb，且此前未与QT间期长度相关联。
结论
我们的结果表明RR间期与GPR133之间存在关联，并证实了QT间期与NOS1AP之间存在关联。
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本文引用的文献
1
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Nat Genet. 2009 Apr;41(4):407-14. doi: 10.1038/ng.362. Epub 2009 Mar 22.
2
Common variants at ten loci influence QT interval duration in the QTGEN Study.在QTGEN研究中，十个基因座上的常见变异影响QT间期持续时间。
Nat Genet. 2009 Apr;41(4):399-406. doi: 10.1038/ng.364. Epub 2009 Mar 22.
3
Common variation in NOS1AP and KCNH2 genes and QT interval duration in young adults. The Cardiovascular Risk in Young Finns Study.一氧化氮合酶1衔接蛋白（NOS1AP）和钾通道亚家族H成员2（KCNH2）基因的常见变异与年轻成年人的QT间期持续时间。芬兰年轻人心血管风险研究。
Ann Med. 2009;41(2):144-51. doi: 10.1080/07853890802392529.
4
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J Biosoc Sci. 2008 Sep;40(5):787-91. doi: 10.1017/s0021932007002568.
5
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Int J Epidemiol. 2008 Oct;37(5):1132-41. doi: 10.1093/ije/dyn091. Epub 2008 May 29.
6
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PLoS One. 2007 Dec 5;2(12):e1274. doi: 10.1371/journal.pone.0001274.
7
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8
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9
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BMC Med Genet. 2007 Sep 19;8 Suppl 1(Suppl 1):S7. doi: 10.1186/1471-2350-8-S1-S7.
10
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