Biobank-driven genomic discovery yields new insight into atrial fibrillation biology.
Biobank-driven genomic discovery yields new insight into atrial fibrillation biology.
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DOI：
10.1038/s41588-018-0171-3
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发表时间：
2018-09
期刊：
影响因子：
30.8
通讯作者：
Willer CJ
中科院分区：
文献类型：
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作者：
Nielsen JB;Thorolfsdottir RB;Fritsche LG;Zhou W;Skov MW;Graham SE;Herron TJ;McCarthy S;Schmidt EM;Sveinbjornsson G;Surakka I;Mathis MR;Yamazaki M;Crawford RD;Gabrielsen ME;Skogholt AH;Holmen OL;Lin M;Wolford BN;Dey R;Dalen H;Sulem P;Chung JH;Backman JD;Arnar DO;Thorsteinsdottir U;Baras A;O'Dushlaine C;Holst AG;Wen X;Hornsby W;Dewey FE;Boehnke M;Kheterpal S;Mukherjee B;Lee S;Kang HM;Holm H;Kitzman J;Shavit JA;Jalife J;Brummett CM;Teslovich TM;Carey DJ;Gudbjartsson DF;Stefansson K;Abecasis GR;Hveem K;Willer CJ
为了确定房颤（最常见的心律失常）的遗传变异，我们对超过1，000，000人进行了全基因组关联研究，其中包括60，620例房颤病例和970，216例对照。我们在111个位点确定了142个独立的风险变异，并优先考虑了151个可能参与房颤的功能候选基因。许多已确定的风险变体位于已报告导致人类严重心脏缺陷的更有害突变的基因（GATA 4，MYH 6，NKX 2 -5，PITX 2，TBX 5）附近，或靠近对横纹肌功能和完整性重要的基因（例如，CFL 2 MYH 7，PKP 2，RBM 20，SGCG，SSPN）。途径和功能富集分析还表明，许多推定的心房颤动基因通过心脏结构重塑发挥作用，可能以“心房心肌病”的形式，在胎儿心脏发育期间或作为对成年心脏应激的反应。
To identify genetic variation underlying atrial fibrillation, the most common cardiac arrhythmia, we performed a genome-wide association study of > 1,000,000 people, including 60,620 atrial fibrillation cases and 970,216 controls. We identified 142 independent risk variants at 111 loci and prioritized 151 functional candidate genes likely to be involved in atrial fibrillation. Many of the identified risk variants fall near genes where more deleterious mutations have been reported to cause serious heart defects in humans (GATA4, MYH6, NKX2–5, PITX2, TBX5), or near genes important for striated muscle function and integrity (for example, CFL2 MYH7, PKP2, RBM20, SGCG, SSPN). Pathway and functional enrichment analyses also suggested that many of the putative atrial fibrillation genes act via cardiac structural remodeling, potentially in the form of an ‘atrial cardiomyopathy’, either during fetal heart development or as a response to stress in the adult heart.
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影响因子：
14.9
作者：
Kanehisa M;Goto S;Sato Y;Furumichi M;Tanabe M
通讯作者：
Tanabe M
影响因子：
46.9
作者：
通讯作者：
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影响因子：
30.8
作者：
Bulik-Sullivan, Brendan K.;Loh, Po-Ru;Finucane, Hilary K.;Ripke, Stephan;Yang, Jian;Patterson, Nick;Daly, Mark J.;Price, Alkes L.;Neale, Benjamin M.
通讯作者：
Neale, Benjamin M.
DOI：
10.1126/science.1262110
发表时间：
2015-05-08
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
GTEx Consortium
通讯作者：
GTEx Consortium
影响因子：
4.8
作者：
Herron, Todd J.;Devaney, Eric;Metzger, Joseph M.
通讯作者：
Metzger, Joseph M.