A rare variant in MYH6 is associated with high risk of sick sinus syndrome

被引：235

作者：

Holm, Hilma ^{[1
]}

Gudbjartsson, Daniel F. ^{[1
]}

Sulem, Patrick ^{[1
]}

Masson, Gisli ^{[1
]}

Helgadottir, Hafdis Th ^{[1
]}

Zanon, Carlo ^{[1
]}

Magnusson, Olafur Th ^{[1
]}

Helgason, Agnar ^{[1
]}

Saemundsdottir, Jona ^{[1
]}

Gylfason, Arnaldur ^{[1
]}

Stefansdottir, Hrafnhildur ^{[2
]}

Gretarsdottir, Solveig ^{[1
]}

Matthiasson, Stefan E. ^{[3
]}

Thorgeirsson, Guomundur ^{[2
,4
]}

Jonasdottir, Aslaug ^{[1
]}

Sigurdsson, Asgeir ^{[1
]}

Stefansson, Hreinn ^{[1
]}

Werge, Thomas ^{[5
]}

Rafnar, Thorunn ^{[1
]}

Kiemeney, Lambertus A. ^{[6
,7
]}

Parvez, Babar ^{[8
]}

Muhammad, Raafia ^{[8
]}

Roden, Dan M. ^{[8
]}

Darbar, Dawood ^{[8
]}

Thorleifsson, Gudmar ^{[1
]}

Walters, G. Bragi ^{[1
]}

Kong, Augustine ^{[1
]}

Thorsteinsdottir, Unnur ^{[1
,4
]}

Arnar, David O. ^{[2
,4
]}

Stefansson, Kari ^{[1
,4
]}

机构：

[1] DeCODE Genet, Reykjavik, Iceland

[2] Landspitali Univ Hosp, Dept Med, Reykjavik, Iceland

[3] Med Clin, Reykjavik, Iceland

[4] Univ Iceland, Fac Med, Reykjavik, Iceland

[5] Copenhagen Univ Hosp, Res Inst Biol Psychiat, Mental Hlth Ctr Sct Hans, Roskilde, Denmark

[6] Radboud Univ Nijmegen, Dept Epidemiol Biostat & Hlth Technol Assessment, Med Ctr, NL-6525 ED Nijmegen, Netherlands

[7] Radboud Univ Nijmegen, Dept Urol, Med Ctr, NL-6525 ED Nijmegen, Netherlands

[8] Vanderbilt Univ, Med Ctr, Dept Med, Nashville, TN USA

来源：

NATURE GENETICS | 2011年 / 43卷 / 04期

基金：

美国国家卫生研究院;

关键词：

MYOSIN HEAVY-CHAIN; GENOME-WIDE ASSOCIATION; SEQUENCE VARIANT; MUTATIONS; EXPRESSION; POPULATIONS; DISEASE;

D O I：

10.1038/ng.781

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

Through complementary application of SNP genotyping, whole-genome sequencing and imputation in 38,384 Icelanders, we have discovered a previously unidentified sick sinus syndrome susceptibility gene, MYH6, encoding the alpha heavy chain subunit of cardiac myosin. A missense variant in this gene, c.2161C > T, results in the conceptual amino acid substitution p.Arg721Trp, has an allelic frequency of 0.38% in Icelanders and associates with sick sinus syndrome with an odds ratio = 12.53 and P = 1.5 x 10(-29). We show that the lifetime risk of being diagnosed with sick sinus syndrome is around 6% for non-carriers of c.2161C > T but is approximately 50% for carriers of the c.2161C > T variant.

引用

页码：316 / U148

页数：8

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