期刊
NATURE GENETICS
卷 45, 期 6, 页码 621-+出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/ng.2610
关键词
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资金
- British Heart Foundation [PG/12/38/29615] Funding Source: Medline
- Medical Research Council [MC_PC_15018, G9815508, G1002084, MC_U127592696, MC_UP_A100_1003, G0801056, MC_U123092720, MC_U106188470, G0600705, MC_U106179471, G0401527, MC_UU_12013/3, MC_PC_U127561128, MC_U106179472, MC_UU_12015/2, MC_PC_U127592696, MC_UU_12013/1, MC_U106179473, MC_UU_12013/4, G1000143] Funding Source: Medline
- NCATS NIH HHS [UL1 TR000124] Funding Source: Medline
- NHLBI NIH HHS [R01 HL111314, R01 HL092217, R01 HL090620, K24 HL105780, R00 HL094535, U19 HL065962, R01 HL105756] Funding Source: Medline
- NIDA NIH HHS [R21 DA026982] Funding Source: Medline
- NIDDK NIH HHS [P30 DK020572, P30 DK063491] Funding Source: Medline
- NIGMS NIH HHS [T32 GM007753] Funding Source: Medline
- Wellcome Trust [092731] Funding Source: Medline
- Chief Scientist Office [CZB/4/710] Funding Source: Medline
- ESRC [ES/J023299/1] Funding Source: UKRI
- MRC [MC_U106179473, G0801056, G1002084, MC_UU_12015/3, MC_U127592696, MC_U123092720, MC_UU_12015/1, MC_U106179472, G0600705, MC_PC_U127592696, MC_UU_12015/2, MC_PC_U127561128, MC_UU_12013/1, MC_UU_12013/3, MR/K013351/1, MC_UU_12013/4, MC_UP_A100_1003, MC_U106188470] Funding Source: UKRI
- British Heart Foundation [PG/12/38/29615] Funding Source: researchfish
- Chief Scientist Office [CZB/4/710] Funding Source: researchfish
- Economic and Social Research Council [ES/J023299/1] Funding Source: researchfish
- Medical Research Council [MC_PC_U127592696, MC_U106179473, MC_U127592696, MC_UU_12013/1, G0801056B, MC_PC_15018, G0401527, MC_UU_12013/3, MC_UU_12015/2, MC_PC_U127561128, MC_U123092720, MC_UU_12015/3, MC_UP_A100_1003, MC_U106188470, G9815508, MC_U106179471, MC_UU_12013/4, MR/K013351/1, G1002084, G0801056, MC_U106179472, G0600705, MC_UU_12015/1, G1000143] Funding Source: researchfish
- National Institute for Health Research [NF-SI-0611-10136, NF-SI-0611-10170] Funding Source: researchfish
- Novo Nordisk Fonden [NNF13OC0005785] Funding Source: researchfish
Elevated resting heart rate is associated with greater risk of cardiovascular disease and mortality. In a 2-stage meta-analysis of genome-wide association studies in up to 181,171 individuals, we identified 14 new loci associated with heart rate and confirmed associations with all 7 previously established loci. Experimental downregulation of gene expression in Drosophila melanogaster and Danio rerio identified 20 genes at 11 loci that are relevant for heart rate regulation and highlight a role for genes involved in signal transmission, embryonic cardiac development and the pathophysiology of dilated cardiomyopathy, congenital heart failure and/or sudden cardiac death. In addition, genetic susceptibility to increased heart rate is associated with altered cardiac conduction and reduced risk of sick sinus syndrome, and both heart rate-increasing and heart rate-decreasing variants associate with risk of atrial fibrillation. Our findings provide fresh insights into the mechanisms regulating heart rate and identify new therapeutic targets.
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