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

van de Vegte, Y.J.; Eppinga, R.N.; van der Ende, M.Y.; Hagemeijer, Y.P.; Mahendran, Y.; Salfati, E.; Smith, A.V.; Tan, V.Y.; Arking, D.E.; Ntalla, I.; Appel, E.V.; Schurmann, C.; Brody, J.A.; Rueedi, R.; Polasek, O.; Sveinbjornsson, G.; Lecoeur, C.; Ladenvall, C.; Zhao, J.H.; Isaacs, A.; Wang, L.; Luan, J.; Hwang, S.J.; Mononen, N.; Auro, K.; Jackson, A.U.; Bielak, L.F.; Zeng, L.; Shah, N.; Nethander, M.; Campbell, A.; Rankinen, T.; Pechlivanis, S.; Qi, L.; Zhao, W.; Rizzi, F.; Tanaka, T.; Robino, A.; Cocca, M.; Lange, L.; Müller-Nurasyid, M.; Roselli, C.; Zhang, W.; Kleber, M.E.; Guo, X.; Lin, H.J.; Pavani, F.; Galesloot, T.E.; Noordam, R.; Milaneschi, Y.; Schraut, K.E.; den Hoed, M.; Degenhardt, F.; Trompet, S.; van den Berg, M.E.; Pistis, G.; Tham, Y.C.; Weiss, S.; Sim, X.S.; Li, H.L.; van der Most, P.J.; Nolte, I.M.; Lyytikäinen, L.P.; Said, M.A.; Witte, D.R.; Iribarren, C.; Launer, L.; Ring, S.M.; de Vries, P.S.; Sever, P.; Linneberg, A.; Bottinger, E.P.; Padmanabhan, S.; Psaty, B.M.; Sotoodehnia, N.; Kolcic, I.; Arnar, D.O.; Gudbjartsson, D.F.; Holm, H.; Balkau, B.; Silva, C.T.; Newton-Cheh, C.H.; Nikus, K.; Salo, P.; Mohlke, K.L.; Peyser, P.A.; Schunkert, H.; Lorentzon, M.; Lahti, J.; Rao, D.C.; Cornelis, M.C.; Faul, J.D.; Smith, J.A.; Stolarz-Skrzypek, K.; Bandinelli, S.; Concas, M.P.; Sinagra, G.; Meitinger, T.; Waldenberger, M.; Sinner, M.F.; Strauch, K.; Delgado, G.E.; Taylor, K.D.; Yao, J.; Foco, L.; Melander, O.; de Graaf, J.; de Mutsert, R.; de Geus, EJC; Johansson, Å.; Joshi, P.K.; Lind, L.; Franke, A.; Macfarlane, P.W.; Tarasov, K.V.; Tan, N.; Felix, S.B.; Tai, E.S.; Quek, D.Q.; Snieder, H.; Ormel, J.; Ingelsson, M.; Lindgren, C.; Morris, A.P.; Raitakari, O.T.; Hansen, T.; Assimes, T.; Gudnason, V.; Timpson, N.J.; Morrison, A.C.; Munroe, P.B.; Strachan, D.P.; Grarup, N.; Loos, RJF; Heckbert, S.R.; Vollenweider, P.; Hayward, C.; Stefansson, K.; Froguel, P.; Groop, L.; Wareham, N.J.; van Duijn, C.M.; Feitosa, M.F.; O'Donnell, C.J.; Kähönen, M.; Perola, M.; Boehnke, M.; Kardia, SLR; Erdmann, J.; Palmer, CNA; Ohlsson, C.; Porteous, D.J.; Eriksson, J.G.; Bouchard, C.; Moebus, S.; Kraft, P.; Weir, D.R.; Cusi, D.; Ferrucci, L.; Ulivi, S.; Girotto, G.; Correa, A.; Kääb, S.; Peters, A.; Chambers, J.C.; Kooner, J.S.; März, W.; Rotter, J.I.; Hicks, A.A.; Smith, J.G.; Kiemeney, LALM; Mook-Kanamori, D.O.; Penninx, BWJH; Gyllensten, U.; Wilson, J.F.; Burgess, S.; Sundström, J.; Lieb, W.; Jukema, J.W.; Eijgelsheim, M.; Lakatta, ELM; Cheng, C.Y.; Dörr, M.; Wong, T.Y.; Sabanayagam, C.; Oldehinkel, A.J.; Riese, H.; Lehtimäki, T.; Verweij, N.; van der Harst, P.

doi:10.1038/s41467-023-39521-2

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

Details

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State: Public
Version: Final published version
License: CC BY 4.0

Serval ID

serval:BIB_3D61EEADF3D4

Type

Article: article from journal or magazin.

Collection

Publications

Institution

UNIL/CHUV

Title

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

Journal

Nature communications

Author(s)

van de Vegte Y.J., Eppinga R.N., van der Ende M.Y., Hagemeijer Y.P., Mahendran Y., Salfati E., Smith A.V., Tan V.Y., Arking D.E., Ntalla I., Appel E.V., Schurmann C., Brody J.A., Rueedi R., Polasek O., Sveinbjornsson G., Lecoeur C., Ladenvall C., Zhao J.H., Isaacs A., Wang L., Luan J., Hwang S.J., Mononen N., Auro K., Jackson A.U., Bielak L.F., Zeng L., Shah N., Nethander M., Campbell A., Rankinen T., Pechlivanis S., Qi L., Zhao W., Rizzi F., Tanaka T., Robino A., Cocca M., Lange L., Müller-Nurasyid M., Roselli C., Zhang W., Kleber M.E., Guo X., Lin H.J., Pavani F., Galesloot T.E., Noordam R., Milaneschi Y., Schraut K.E., den Hoed M., Degenhardt F., Trompet S., van den Berg M.E., Pistis G., Tham Y.C., Weiss S., Sim X.S., Li H.L., van der Most P.J., Nolte I.M., Lyytikäinen L.P., Said M.A., Witte D.R., Iribarren C., Launer L., Ring S.M., de Vries P.S., Sever P., Linneberg A., Bottinger E.P., Padmanabhan S., Psaty B.M., Sotoodehnia N., Kolcic I., Arnar D.O., Gudbjartsson D.F., Holm H., Balkau B., Silva C.T., Newton-Cheh C.H., Nikus K., Salo P., Mohlke K.L., Peyser P.A., Schunkert H., Lorentzon M., Lahti J., Rao D.C., Cornelis M.C., Faul J.D., Smith J.A., Stolarz-Skrzypek K., Bandinelli S., Concas M.P., Sinagra G., Meitinger T., Waldenberger M., Sinner M.F., Strauch K., Delgado G.E., Taylor K.D., Yao J., Foco L., Melander O., de Graaf J., de Mutsert R., de Geus EJC, Johansson Å., Joshi P.K., Lind L., Franke A., Macfarlane P.W., Tarasov K.V., Tan N., Felix S.B., Tai E.S., Quek D.Q., Snieder H., Ormel J., Ingelsson M., Lindgren C., Morris A.P., Raitakari O.T., Hansen T., Assimes T., Gudnason V., Timpson N.J., Morrison A.C., Munroe P.B., Strachan D.P., Grarup N., Loos RJF, Heckbert S.R., Vollenweider P., Hayward C., Stefansson K., Froguel P., Groop L., Wareham N.J., van Duijn C.M., Feitosa M.F., O'Donnell C.J., Kähönen M., Perola M., Boehnke M., Kardia SLR, Erdmann J., Palmer CNA, Ohlsson C., Porteous D.J., Eriksson J.G., Bouchard C., Moebus S., Kraft P., Weir D.R., Cusi D., Ferrucci L., Ulivi S., Girotto G., Correa A., Kääb S., Peters A., Chambers J.C., Kooner J.S., März W., Rotter J.I., Hicks A.A., Smith J.G., Kiemeney LALM, Mook-Kanamori D.O., Penninx BWJH, Gyllensten U., Wilson J.F., Burgess S., Sundström J., Lieb W., Jukema J.W., Eijgelsheim M., Lakatta ELM, Cheng C.Y., Dörr M., Wong T.Y., Sabanayagam C., Oldehinkel A.J., Riese H., Lehtimäki T., Verweij N., van der Harst P.

Working group(s)

DCCT/EDIC Research Group

Contributor(s)

Roshandel D., Paterson A.D.

ISSN

2041-1723 (Electronic)

ISSN-L

2041-1723

Publication state

Published

Issued date

02/08/2023

Peer-reviewed

Oui

Volume

Number

Pages

4646

Language

english

Notes

Publication types: Meta-Analysis ; Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: epublish

Abstract

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.

Keywords

Humans, Cardiovascular Diseases/genetics, Risk Factors, Heart Rate/genetics, Genetic Predisposition to Disease, Atrial Fibrillation, Mendelian Randomization Analysis/methods, Genome-Wide Association Study/methods, Polymorphism, Single Nucleotide

URN

urn:nbn:ch:serval-BIB_3D61EEADF3D40

OAI-PMH

oai:serval.unil.ch:BIB_3D61EEADF3D4

DOI

10.1038/s41467-023-39521-2

Pubmed

37532724

Web of science

001042222000014

Open Access

Yes