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

Title:	Genetic insights into resting heart rate and its role in cardiovascular disease.
Authors:	van de Vegte, YJ; Eppinga, RN; van der Ende, MY; Hagemeijer, YP; Mahendran, Y; Salfati, E; Smith, AV; Tan, VY; Arking, DE; Ntalla, I; Appel, EV; Schurmann, C; Brody, JA; Rueedi, R; Polasek, O; Sveinbjornsson, G; Lecoeur, C; Ladenvall, C; Zhao, JH; Isaacs, A; Wang, L; Luan, J; Hwang, S-J; Mononen, N; Auro, K; Jackson, AU; Bielak, LF; 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, ME; Guo, X; Lin, HJ; Pavani, F; Galesloot, TE; Noordam, R; Milaneschi, Y; Schraut, KE; den Hoed, M; Degenhardt, F; Trompet, S; van den Berg, ME; Pistis, G; Tham, Y-C; Weiss, S; Sim, XS; Li, HL; van der Most, PJ; Nolte, IM; Lyytikäinen, L-P; Said, MA; Witte, DR; Iribarren, C; Launer, L; Ring, SM; de Vries, PS; Sever, P; Linneberg, A; Bottinger, EP; Padmanabhan, S; Psaty, BM; Sotoodehnia, N; Kolcic, I; DCCT/EDIC Research Group; Arnar, DO; Gudbjartsson, DF; Holm, H; Balkau, B; Silva, CT; Newton-Cheh, CH; Nikus, K; Salo, P; Mohlke, KL; Peyser, PA; Schunkert, H; Lorentzon, M; Lahti, J; Rao, DC; Cornelis, MC; Faul, JD; Smith, JA; Stolarz-Skrzypek, K; Bandinelli, S; Concas, MP; Sinagra, G; Meitinger, T; Waldenberger, M; Sinner, MF; Strauch, K; Delgado, GE; Taylor, KD; Yao, J; Foco, L; Melander, O; de Graaf, J; de Mutsert, R; de Geus, EJC; Johansson, Å; Joshi, PK; Lind, L; Franke, A; Macfarlane, PW; Tarasov, KV; Tan, N; Felix, SB; Tai, E-S; Quek, DQ; Snieder, H; Ormel, J; Ingelsson, M; Lindgren, C; Morris, AP; Raitakari, OT; Hansen, T; Assimes, T; Gudnason, V; Timpson, NJ; Morrison, AC; Munroe, PB; Strachan, DP; Grarup, N; Loos, RJF; Heckbert, SR; Vollenweider, P; Hayward, C; Stefansson, K; Froguel, P; Groop, L; Wareham, NJ; van Duijn, CM; Feitosa, MF; O'Donnell, CJ; Kähönen, M; Perola, M; Boehnke, M; Kardia, SLR; Erdmann, J; Palmer, CNA; Ohlsson, C; Porteous, DJ; Eriksson, JG; Bouchard, C; Moebus, S; Kraft, P; Weir, DR; Cusi, D; Ferrucci, L; Ulivi, S; Girotto, G; Correa, A; Kääb, S; Peters, A; Chambers, JC; Kooner, JS; März, W; Rotter, JI; Hicks, AA; Smith, JG; Kiemeney, LALM; Mook-Kanamori, DO; Penninx, BWJH; Gyllensten, U; Wilson, JF; Burgess, S; Sundström, J; Lieb, W; Jukema, JW; Eijgelsheim, M; Lakatta, ELM; Cheng, C-Y; Dörr, M; Wong, T-Y; Sabanayagam, C; Oldehinkel, AJ; Riese, H; Lehtimäki, T; Verweij, N; van der Harst, P
Publisher Information:	Nature Research
Publication Year:	2023
Collection:	St George's University of London: Repository
Description:	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.
Document Type:	article in journal/newspaper
File Description:	application/pdf; application/vnd.openxmlformats-officedocument.wordprocessingml.document; application/vnd.ms-excel
Language:	English
ISSN:	2041-1723
Relation:	https://openaccess.sgul.ac.uk/id/eprint/115488/17/s41467-023-39521-2.pdf; https://openaccess.sgul.ac.uk/id/eprint/115488/22/41467_2023_39521_MOESM1_ESM.docx; https://openaccess.sgul.ac.uk/id/eprint/115488/24/41467_2023_39521_MOESM2_ESM.pdf; https://openaccess.sgul.ac.uk/id/eprint/115488/29/41467_2023_39521_MOESM3_ESM.pdf; https://openaccess.sgul.ac.uk/id/eprint/115488/34/41467_2023_39521_MOESM4_ESM.xlsx; https://openaccess.sgul.ac.uk/id/eprint/115488/35/41467_2023_39521_MOESM5_ESM.pdf; https://openaccess.sgul.ac.uk/id/eprint/115488/1/NCOMMS-22-22457C_Main_paper.pdf; https://openaccess.sgul.ac.uk/id/eprint/115488/6/NCOMMS-22-22457C_Figures.pdf; https://openaccess.sgul.ac.uk/id/eprint/115488/11/NCOMMS-22-22457C_Supplementary_Information.pdf; https://openaccess.sgul.ac.uk/id/eprint/115488/16/NCOMMS-22-22457C_Supplementary_Data.xlsx; van de Vegte, YJ; Eppinga, RN; van der Ende, MY; Hagemeijer, YP; Mahendran, Y; Salfati, E; Smith, AV; Tan, VY; Arking, DE; Ntalla, I; et al. van de Vegte, YJ; Eppinga, RN; van der Ende, MY; Hagemeijer, YP; Mahendran, Y; Salfati, E; Smith, AV; Tan, VY; Arking, DE; Ntalla, I; Appel, EV; Schurmann, C; Brody, JA; Rueedi, R; Polasek, O; Sveinbjornsson, G; Lecoeur, C; Ladenvall, C; Zhao, JH; Isaacs, A; Wang, L; Luan, J; Hwang, S-J; Mononen, N; Auro, K; Jackson, AU; Bielak, LF; 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, ME; Guo, X; Lin, HJ; Pavani, F; Galesloot, TE; Noordam, R; Milaneschi, Y; Schraut, KE; den Hoed, M; Degenhardt, F; Trompet, S; van den Berg, ME; Pistis, G; Tham, Y-C; Weiss, S; Sim, XS; Li, HL; van der Most, PJ; Nolte, IM; Lyytikäinen, L-P; Said, MA; Witte, DR; Iribarren, C; Launer, L; Ring, SM; de Vries, PS; Sever, P; Linneberg, A; Bottinger, EP; Padmanabhan, S; Psaty, BM; Sotoodehnia, N; Kolcic, I; DCCT/EDIC Research Group; Arnar, DO; Gudbjartsson, DF; Holm, H; Balkau, B; Silva, CT; Newton-Cheh, CH; Nikus, K; Salo, P; Mohlke, KL; Peyser, PA; Schunkert, H; Lorentzon, M; Lahti, J; Rao, DC; Cornelis, MC; Faul, JD; Smith, JA; Stolarz-Skrzypek, K; Bandinelli, S; Concas, MP; Sinagra, G; Meitinger, T; Waldenberger, M; Sinner, MF; Strauch, K; Delgado, GE; Taylor, KD; Yao, J; Foco, L; Melander, O; de Graaf, J; de Mutsert, R; de Geus, EJC; Johansson, Å; Joshi, PK; Lind, L; Franke, A; Macfarlane, PW; Tarasov, KV; Tan, N; Felix, SB; Tai, E-S; Quek, DQ; Snieder, H; Ormel, J; Ingelsson, M; Lindgren, C; Morris, AP; Raitakari, OT; Hansen, T; Assimes, T; Gudnason, V; Timpson, NJ; Morrison, AC; Munroe, PB; Strachan, DP; Grarup, N; Loos, RJF; Heckbert, SR; Vollenweider, P; Hayward, C; Stefansson, K; Froguel, P; Groop, L; Wareham, NJ; van Duijn, CM; Feitosa, MF; O'Donnell, CJ; Kähönen, M; Perola, M; Boehnke, M; Kardia, SLR; Erdmann, J; Palmer, CNA; Ohlsson, C; Porteous, DJ; Eriksson, JG; Bouchard, C; Moebus, S; Kraft, P; Weir, DR; Cusi, D; Ferrucci, L; Ulivi, S; Girotto, G; Correa, A; Kääb, S; Peters, A; Chambers, JC; Kooner, JS; März, W; Rotter, JI; Hicks, AA; Smith, JG; Kiemeney, LALM; Mook-Kanamori, DO; Penninx, BWJH; Gyllensten, U; Wilson, JF; Burgess, S; Sundström, J; Lieb, W; Jukema, JW; Eijgelsheim, M; Lakatta, ELM; Cheng, C-Y; Dörr, M; Wong, T-Y; Sabanayagam, C; Oldehinkel, AJ; Riese, H; Lehtimäki, T; Verweij, N; van der Harst, P (2023) Genetic insights into resting heart rate and its role in cardiovascular disease. Nat Commun, 14 (1). p. 4646. ISSN 2041-1723 https://doi.org/10.1038/s41467-023-39521-2 SGUL Authors: Strachan, David Peter
DOI:	10.1038/s41467-023-39521-2
Availability:	https://openaccess.sgul.ac.uk/id/eprint/115488/; https://openaccess.sgul.ac.uk/id/eprint/115488/22/41467_2023_39521_MOESM1_ESM.docx; https://openaccess.sgul.ac.uk/id/eprint/115488/24/41467_2023_39521_MOESM2_ESM.pdf; https://openaccess.sgul.ac.uk/id/eprint/115488/29/41467_2023_39521_MOESM3_ESM.pdf; https://openaccess.sgul.ac.uk/id/eprint/115488/34/41467_2023_39521_MOESM4_ESM.xlsx; https://openaccess.sgul.ac.uk/id/eprint/115488/35/41467_2023_39521_MOESM5_ESM.pdf; https://doi.org/10.1038/s41467-023-39521-2
Rights:	cc_by_4
Accession Number:	edsbas.2BF173B7
Database:	BASE