Genetic insights into resting heart rate and its role in cardiovascular disease

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Abstract Ämnesord

Stäng

The genetics and clinical consequences of resting heart rate (RHR) remain incompletely understood. Here, the authors discover new genetic variants associated with RHR and find that higher genetically predicted RHR decreases risk of atrial fibrillation and ischemic stroke. Resting heart rate is associated with cardiovascular diseases and mortality in observational and Mendelian randomization studies. The aims of this study are to extend the number of resting heart rate associated genetic variants and to obtain further insights in resting heart rate biology and its clinical consequences. A genome-wide meta-analysis of 100 studies in up to 835,465 individuals reveals 493 independent genetic variants in 352 loci, including 68 genetic variants outside previously identified resting heart rate associated loci. We prioritize 670 genes and in silico annotations point to their enrichment in cardiomyocytes and provide insights in their ECG signature. Two-sample Mendelian randomization analyses indicate that higher genetically predicted resting heart rate increases risk of dilated cardiomyopathy, but decreases risk of developing atrial fibrillation, ischemic stroke, and cardio-embolic stroke. We do not find evidence for a linear or non-linear genetic association between resting heart rate and all-cause mortality in contrast to our previous Mendelian randomization study. Systematic alteration of key differences between the current and previous Mendelian randomization study indicates that the most likely cause of the discrepancy between these studies arises from false positive findings in previous one-sample MR analyses caused by weak-instrument bias at lower P-value thresholds. The results extend our understanding of resting heart rate biology and give additional insights in its role in cardiovascular disease development.

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Kardiologi (hsv//swe)
MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Cardiac and Cardiovascular Systems (hsv//eng)
MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Medicinsk genetik (hsv//swe)
MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Medical Genetics (hsv//eng)

Nyckelord

Atrial Fibrillation
Cardiovascular Diseases
Genetic Predisposition to Disease
Genome-Wide Association Study
Heart Rate
Humans
Mendelian Randomization Analysis
Polymorphism, Single Nucleotide
Risk Factors
cardiovascular disease
cardiovascular system
meta-analysis
mortality
sampling
atrial fibrillation
genetic predisposition
genetics
genome-wide association study
heart rate
human
Mendelian randomization analysis
meta analysis
procedures
risk factor
single nucleotide polymorphism

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Av författaren/redakt...: van de Vegte, Yo ...; Eppinga, Ruben P ...; van der Ende, M. ...; Hagemeijer, Yani ...; Mahendran, Yuvar ...; Salfati, Elias Y ...; visa fler...; Smith, Albert E.; Tan, Vanessa; Arking, Dan V.; Ntalla, Ioanna; Appel, Emil A.; Schurmann, Claud ...; Brody, Jennifer; Rueedi, Rico; Polasek, Ozren; Sveinbjornsson, ...; Lecoeur, Cecile; Ladenvall, Claes ...; Zhao, Jing Hua; Isaacs, Aaron; Wang, Lihua; Luan, Jian'an; Hwang, Shih-Jen; Mononen, Nina U.; Auro, Kirsi F.; Jackson, Anne; Bielak, Lawrence; Zeng, Linyao; Shah, Nabi; Nethander, Maria ...; Campbell, Archie; Rankinen, Tuomo; Pechlivanis, Son ...; Qi, Lu; Zhao, Wei; Rizzi, Federica; Tanaka, Toshiko; Robino, Antoniet ...; Cocca, Massimili ...; Groop, L.; Mueller-Nurasyid ...; Roselli, Carolin ...; Zhang, Weihua; Kleber, Marcus J ...; Guo, Xiuqing; Lin, Henry E.; Pavani, Francesc ...; Galesloot, Tesse ...; Noordam, Raymond ...; Milaneschi, Yuri; Schraut, Kathari ...; den Hoed, Marcel ...; Degenhardt, Frau ...; Trompet, Stella; van den Berg, Ma ...; Pistis, Giorgio; Tham, Yih-Chung ...; Weiss, Stefan L.; Sim, Xueling J.; Li, Hengtong M.; van der Most, Pe ...; Nolte, Ilja; Lyytikaeinen, Le ...; Said, M. Abdulla ...; Witte, Daniel; Iribarren, Carlo ...; Launer, Lenore S ...; Ring, Susan; de Vries, Paul; Sever, Peter P.; Linneberg, Allan; Bottinger, Erwin ...; Padmanabhan, San ...; Psaty, Bruce; Sotoodehnia, Non ...; Kolcic, Ivana; Roshandel, Delna ...; Paterson, Andrew ...; Arnar, David F.; Gudbjartsson, Da ...; Holm, Hilma; Balkau, Beverley ...; Silva, Claudia H ...; Newton-Cheh, Chr ...; Nikus, Kjell; Salo, Perttu L.; Mohlke, Karen A.; Peyser, Patricia; Schunkert, Herib ...; Lorentzon, Matti ...; Lahti, Jari C.; Rao, Dabeeru C.; Cornelis, Marily ...; Faul, Jessica A.; Smith, J.G.; Stolarz-Skrzypek ...; Bandinelli, Stef ...; Concas, Maria Pi ...; Sinagra, Gianfra ...; Meitinger, Thoma ...; Waldenberger, Me ...; Sinner, Moritz; Strauch, Konstan ...; Delgado, Graciel ...; Taylor, Kent; Yao, Jie; Foco, Luisa; Melander, O.; de Graaf, Jacque ...; de Mutsert, Rene ...; de Geus, Eco J. ...; Johansson, Åsa; Joshi, Peter K.; Lind, Lars; Franke, Andre W.; Macfarlane, Pete ...; Tarasov, Kirill; Tan, Nicholas B.; Felix, Stephan; Tai, E-Shyong Q.; Quek, Debra; Snieder, Harold; Ormel, Johan; Ingelsson, Marti ...; Lindgren, Cecili ...; Morris, Andrew T ...; Raitakari, Olli; Hansen, Torben; Assimes, Themist ...; Gudnason, Vilmun ...; Timpson, Nichola ...; Morrison, Alanna ...; Munroe, Patricia ...; Strachan, David; Grarup, Niels; Loos, Ruth J. F. ...; Heckbert, Susan; Vollenweider, Pe ...; Hayward, Carolin ...; Stefansson, Kari; Froguel, Philipp ...; Groop, Leif J.; Wareham, Nichola ...; van Duijn, Corne ...; Feitosa, Mary J.; O'Donnell, Chris ...; Kaehoenen, Mika; Perola, Markus; Boehnke, Michael; Kardia, Sharon L ...; Erdmann, Jeanett ...; Palmer, Colin N. ...; Ohlsson, Claes J ...; Porteous, David ...; Eriksson, Johan; Bouchard, Claude; Moebus, Susanne; Kraft, Peter R.; Weir, David; Cusi, Daniele; Ferrucci, Luigi; Ulivi, Sheila; Girotto, Giorgia; Correa, Adolfo; Kaeaeb, Stefan; Peters, Annette ...; Chambers, John S ...; Kooner, Jaspal; Maerz, Winfried ...; Rotter, Jerome A ...; Hicks, Andrew; Smith, J. Gustav; Kiemeney, Lamber ...; Mook-Kanamori, D ...; Penninx, Brenda ...; Gyllensten, Ulf; Wilson, James; Burgess, Stephen; Sundström, Johan ...; Lieb, Wolfgang; Jukema, J. Woute ...; Eijgelsheim, Mar ...; Lakatta, Edward ...; Cheng, Ching-Yu; Doerr, Marcus; Wong, Tien-Yin; Sabanayagam, Cha ...; Oldehinkel, Albe ...; Riese, Harriette; Lehtimaeki, Terh ...; Verweij, Niek; van der Harst, P ...; Eppinga, Ruben N; Smith, Albert V; Arking, Dan E; Kleber, Marcus E; Lin, Henry J; Sim, Xueling S; Arnar, David O; Cornelis, Marily ...; Faul, Jessica D; Smith, Jennifer ...; Timpson, Nichola ...; Morrison, Alanna ...; Wareham, Nichola ...; Feitosa, Mary F; Porteous, David ...; Kääb, Stefan; Rotter, Jerome I; visa färre...

Om ämnet

MEDICIN OCH HÄLSOVETENSKAP: MEDICIN OCH HÄLS ...; och Klinisk medicin; och Kardiologi

MEDICIN OCH HÄLSOVETENSKAP: MEDICIN OCH HÄLS ...; och Medicinska och f ...; och Medicinsk geneti ...

Artiklar i publikationen: Nature Communica ...

Av lärosätet: Uppsala universitet; Lunds universitet; Göteborgs universitet

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