Genome-wide association study of PR interval.
Genome-wide association study of PR interval.
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心电图PR间期反映心房和房室结传导，其紊乱会增加房颤（AF）的风险。为了确定潜在的共同遗传变异，我们荟元分析了CHARGE联盟中7个基于社区的欧洲血统个体的PR间隔的全基因组关联结果：AGES， ARIC， CHS， FHS， KORA，鹿特丹研究和撒丁岛（N=28,517）。检测具有统计学意义的位点（P<5×10-8）与AF的相关性（N=5,741例）。我们确定了9个与PR间隔相关的位点。在3p22.2染色体上，我们观察到电压门控钠通道基因SCN10A和SCN5A有两个独立的关联，而心脏发育基因CAV1/CAV2、NKX2-5 （CSX1）、SOX5、WNT11、MEIS1和TBX5/TBX3附近有6个位点。另一个信号位于ARHGAP24位点，这个位点与心脏没有已知的相关性。9个位点中的5个位点SCN5A、SCN10A、NKX2-5、CAV1/CAV2和SOX5也与AF相关（P<0.0056）。常见的遗传变异，特别是离子通道和发育基因，对心房和房室传导和房颤风险有重要影响。
The electrocardiographic PR interval reflects atrial and atrioventricular nodal conduction, disturbances of which increase risk of atrial fibrillation (AF). To identify underlying common genetic variation, we meta-analyzed genome-wide association results for PR interval from seven community-based studies of European-ancestry individuals in the CHARGE consortium: AGES, ARIC, CHS, FHS, KORA, Rotterdam Study, and SardiNIA (N=28,517). Statistically significant loci (P<5×10-8) were tested for association with AF (N=5,741 cases). We identified nine loci associated with PR interval. At chromosome 3p22.2, we observed two independent associations in voltage gated sodium channel genes SCN10A and SCN5A, while six loci were near cardiac developmental genes CAV1/CAV2, NKX2-5 (CSX1), SOX5, WNT11, MEIS1, and TBX5/TBX3. Another signal was at ARHGAP24, a locus without known relevance to the heart. Five of the nine loci, SCN5A, SCN10A, NKX2-5, CAV1/CAV2, and SOX5, were also associated with AF (P<0.0056). Common genetic variation, particularly in ion channel and developmental genes, contributes significantly to atrial and atrioventricular conduction and to AF risk.
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影响因子：
2.8
作者：
HANSON, B;TUNA, N;RICH, S
通讯作者：
RICH, S
影响因子：
1.3
作者：
HAVLIK, RJ;GARRISON, RJ;FEINLEIB, M
通讯作者：
FEINLEIB, M
影响因子：
30.8
作者：
Arking, Dan E.;Pfeufer, Arne;Chakravarti, Aravinda
通讯作者：
Chakravarti, Aravinda
影响因子：
37.8
作者：
Chung, MK;Martin, DO;Van Wagoner, DR
通讯作者：
Van Wagoner, DR
影响因子：
9.8
作者：
Chen, Wei-Min;Abecasis, Goncalo R.
通讯作者：
Abecasis, Goncalo R.