Genetic loci associated with heart rate variability and their effects on cardiac disease risk

Ilja M. Nolte; M. Loretto Munoz; Vinicius Tragante; Azmeraw T. Amare; Rick Jansen; Ahmad Vaez; Benedikt Von Der Heyde; Christy L. Avery; Joshua C. Bis; Bram Dierckx; Jenny Van Dongen; Stephanie M. Gogarten; Philippe Goyette; Jussi Hernesniemi; Ville Huikari; Shih Jen Hwang; Deepali Jaju; Kathleen F. Kerr; Alexander Kluttig; Bouwe P. Krijthe; Jitender Kumar; Sander W. Van Der Laan; Leo Pekka Lyytikäinen; Adam X. Maihofer; Arpi Minassian; Peter J. Van Der Most; Martina Müller-Nurasyid; Michel Nivard; Erika Salvi; James D. Stewart; Julian F. Thayer; Niek Verweij; Andrew Wong; Delilah Zabaneh; Mohammad H. Zafarmand; Abdel Abdellaoui; Sulayma Albarwani; Christine Albert; Alvaro Alonso; Foram Ashar; Juha Auvinen; Tomas Axelsson; Dewleen G. Baker; Paul I.W. De Bakker; Matteo Barcella; Riad Bayoumi; Rob J. Bieringa; Dorret Boomsma; Gabrielle Boucher; Annie R. Britton; Ingrid E. Christophersen; Andrea Dietrich; George B. Ehret; Patrick T. Ellinor; Markku Eskola; Janine F. Felix; John S. Floras; Oscar H. Franco; Peter Friberg; Maaike G.J. Gademan; Mark A. Geyer; Vilmantas Giedraitis; Catharina A. Hartman; Daiane Hemerich; Albert Hofman; Jouke Jan Hottenga; Heikki Huikuri; Nina Hutri-Kähönen; Xavier Jouven; Juhani Junttila; Markus Juonala; Antti M. Kiviniemi; Jan A. Kors; Meena Kumari; Tatiana Kuznetsova; Cathy C. Laurie; Joop D. Lefrandt; Yong Li; Yun Li; Duanping Liao; Marian C. Limacher; Henry J. Lin; Cecilia M. Lindgren; Steven A. Lubitz; Anubha Mahajan; Barbara McKnight; Henriette Meyer Zu Schwabedissen; Yuri Milaneschi; Nina Mononen; Andrew P. Morris; Mike A. Nalls; Gerjan Navis; Melanie Neijts; Kjell Nikus; Kari E. North; Daniel T. O'Connor; Johan Ormel; Siegfried Perz; Annette Peters; Bruce M. Psaty; Olli T. Raitakari; Victoria B. Risbrough; Moritz F. Sinner; David Siscovick; Johannes H. Smit; Nicholas L. Smith; Elsayed Z. Soliman; Nona Sotoodehnia; Jan A. Staessen; Phyllis K. Stein; Adrienne M. Stilp; Katarzyna Stolarz-Skrzypek; Konstantin Strauch; Johan Sundström; Cees A. Swenne; Ann Christine Syvänen; Jean Claude Tardif; Kent D. Taylor; Alexander Teumer; Timothy A. Thornton; Lesley E. Tinker; André G. Uitterlinden; Jessica Van Setten; Andreas Voss; Melanie Waldenberger; Kirk C. Wilhelmsen; Gonneke Willemsen; Quenna Wong; Zhu Ming Zhang; Alan B. Zonderman; Daniele Cusi; Michele K. Evans; Halina K. Greiser; Pim Van Der Harst; Mohammad Hassan; Erik Ingelsson; Marjo Riitta Järvelin; Stefan Kääb; Mika Kähönen; Mika Kivimaki; Charles Kooperberg; Diana Kuh; Terho Lehtimäki; Lars Lind; Caroline M. Nievergelt; Chris J. O'Donnell; Albertine J. Oldehinkel; Brenda Penninx; Alexander P. Reiner; Harriëtte Riese; Arie M. Van Roon; John D. Rioux; Jerome I. Rotter; Tamar Sofer; Bruno H. Stricker; Henning Tiemeier; Tanja G.M. Vrijkotte; Folkert W. Asselbergs; Bianca J.J.M. Brundel; Susan R. Heckbert; Eric A. Whitsel; Marcel Den Hoed; Harold Snieder; Eco J.C. De Geus

doi:10.1038/ncomms15805

Genetic loci associated with heart rate variability and their effects on cardiac disease risk

Ilja M. Nolte^*, M. Loretto Munoz, Vinicius Tragante, Azmeraw T. Amare, Rick Jansen, Ahmad Vaez, Benedikt Von Der Heyde, Christy L. Avery, Joshua C. Bis, Bram Dierckx, Jenny Van Dongen, Stephanie M. Gogarten, Philippe Goyette, Jussi Hernesniemi, Ville Huikari, Shih Jen Hwang, Deepali Jaju, Kathleen F. Kerr, Alexander Kluttig, Bouwe P. KrijtheJitender Kumar, Sander W. Van Der Laan, Leo Pekka Lyytikäinen, Adam X. Maihofer, Arpi Minassian, Peter J. Van Der Most, Martina Müller-Nurasyid, Michel Nivard, Erika Salvi, James D. Stewart, Julian F. Thayer, Niek Verweij, Andrew Wong, Delilah Zabaneh, Mohammad H. Zafarmand, Abdel Abdellaoui, Sulayma Albarwani, Christine Albert, Alvaro Alonso, Foram Ashar, Juha Auvinen, Tomas Axelsson, Dewleen G. Baker, Paul I.W. De Bakker, Matteo Barcella, Riad Bayoumi, Rob J. Bieringa, Dorret Boomsma, Gabrielle Boucher, Annie R. Britton, Ingrid E. Christophersen, Andrea Dietrich, George B. Ehret, Patrick T. Ellinor, Markku Eskola, Janine F. Felix, John S. Floras, Oscar H. Franco, Peter Friberg, Maaike G.J. Gademan, Mark A. Geyer, Vilmantas Giedraitis, Catharina A. Hartman, Daiane Hemerich, Albert Hofman, Jouke Jan Hottenga, Heikki Huikuri, Nina Hutri-Kähönen, Xavier Jouven, Juhani Junttila, Markus Juonala, Antti M. Kiviniemi, Jan A. Kors, Meena Kumari, Tatiana Kuznetsova, Cathy C. Laurie, Joop D. Lefrandt, Yong Li, Yun Li, Duanping Liao, Marian C. Limacher, Henry J. Lin, Cecilia M. Lindgren, Steven A. Lubitz, Anubha Mahajan, Barbara McKnight, Henriette Meyer Zu Schwabedissen, Yuri Milaneschi, Nina Mononen, Andrew P. Morris, Mike A. Nalls, Gerjan Navis, Melanie Neijts, Kjell Nikus, Kari E. North, Daniel T. O'Connor, Johan Ormel, Siegfried Perz, Annette Peters, Bruce M. Psaty, Olli T. Raitakari, Victoria B. Risbrough, Moritz F. Sinner, David Siscovick, Johannes H. Smit, Nicholas L. Smith, Elsayed Z. Soliman, Nona Sotoodehnia, Jan A. Staessen, Phyllis K. Stein, Adrienne M. Stilp, Katarzyna Stolarz-Skrzypek, Konstantin Strauch, Johan Sundström, Cees A. Swenne, Ann Christine Syvänen, Jean Claude Tardif, Kent D. Taylor, Alexander Teumer, Timothy A. Thornton, Lesley E. Tinker, André G. Uitterlinden, Jessica Van Setten, Andreas Voss, Melanie Waldenberger, Kirk C. Wilhelmsen, Gonneke Willemsen, Quenna Wong, Zhu Ming Zhang, Alan B. Zonderman, Daniele Cusi, Michele K. Evans, Halina K. Greiser, Pim Van Der Harst, Mohammad Hassan, Erik Ingelsson, Marjo Riitta Järvelin, Stefan Kääb, Mika Kähönen, Mika Kivimaki, Charles Kooperberg, Diana Kuh, Terho Lehtimäki, Lars Lind, Caroline M. Nievergelt, Chris J. O'Donnell, Albertine J. Oldehinkel, Brenda Penninx, Alexander P. Reiner, Harriëtte Riese, Arie M. Van Roon, John D. Rioux, Jerome I. Rotter, Tamar Sofer, Bruno H. Stricker, Henning Tiemeier, Tanja G.M. Vrijkotte, Folkert W. Asselbergs, Bianca J.J.M. Brundel, Susan R. Heckbert, Eric A. Whitsel, Marcel Den Hoed, Harold Snieder, Eco J.C. De Geus

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

Abstract

Reduced cardiac vagal control reflected in low heart rate variability (HRV) is associated with greater risks for cardiac morbidity and mortality. In two-stage meta-analyses of genome-wide association studies for three HRV traits in up to 53,174 individuals of European ancestry, we detect 17 genome-wide significant SNPs in eight loci. HRV SNPs tag non-synonymous SNPs (in NDUFA11 and KIAA1755), expression quantitative trait loci (eQTLs) (influencing GNG11, RGS6 and NEO1), or are located in genes preferentially expressed in the sinoatrial node (GNG11, RGS6 and HCN4). Genetic risk scores account for 0.9 to 2.6% of the HRV variance. Significant genetic correlation is found for HRV with heart rate (-0.74<r g <-0.55) and blood pressure (-0.35<r g <-0.20). These findings provide clinically relevant biological insight into heritable variation in vagal heart rhythm regulation, with a key role for genetic variants (GNG11, RGS6) that influence G-protein heterotrimer action in GIRK-channel induced pacemaker membrane hyperpolarization.

Original language	English
Article number	15805
Journal	Nature Communications
Volume	8
DOIs	https://doi.org/10.1038/ncomms15805
Publication status	Published - 14 Jun 2017

Access to Document

10.1038/ncomms15805

Cite this

Nolte, I. M., Munoz, M. L., Tragante, V., Amare, A. T., Jansen, R., Vaez, A., Von Der Heyde, B., Avery, C. L., Bis, J. C., Dierckx, B., Van Dongen, J., Gogarten, S. M., Goyette, P., Hernesniemi, J., Huikari, V., Hwang, S. J., Jaju, D., Kerr, K. F., Kluttig, A., ... De Geus, E. J. C. (2017). Genetic loci associated with heart rate variability and their effects on cardiac disease risk. Nature Communications, 8, [15805]. https://doi.org/10.1038/ncomms15805

@article{812ebaf860cf4de98b28a2549195b0a4,

title = "Genetic loci associated with heart rate variability and their effects on cardiac disease risk",

abstract = "Reduced cardiac vagal control reflected in low heart rate variability (HRV) is associated with greater risks for cardiac morbidity and mortality. In two-stage meta-analyses of genome-wide association studies for three HRV traits in up to 53,174 individuals of European ancestry, we detect 17 genome-wide significant SNPs in eight loci. HRV SNPs tag non-synonymous SNPs (in NDUFA11 and KIAA1755), expression quantitative trait loci (eQTLs) (influencing GNG11, RGS6 and NEO1), or are located in genes preferentially expressed in the sinoatrial node (GNG11, RGS6 and HCN4). Genetic risk scores account for 0.9 to 2.6% of the HRV variance. Significant genetic correlation is found for HRV with heart rate (-0.74",

author = "Nolte, {Ilja M.} and Munoz, {M. Loretto} and Vinicius Tragante and Amare, {Azmeraw T.} and Rick Jansen and Ahmad Vaez and {Von Der Heyde}, Benedikt and Avery, {Christy L.} and Bis, {Joshua C.} and Bram Dierckx and {Van Dongen}, Jenny and Gogarten, {Stephanie M.} and Philippe Goyette and Jussi Hernesniemi and Ville Huikari and Hwang, {Shih Jen} and Deepali Jaju and Kerr, {Kathleen F.} and Alexander Kluttig and Krijthe, {Bouwe P.} and Jitender Kumar and {Van Der Laan}, {Sander W.} and Lyytik{\"a}inen, {Leo Pekka} and Maihofer, {Adam X.} and Arpi Minassian and {Van Der Most}, {Peter J.} and Martina M{\"u}ller-Nurasyid and Michel Nivard and Erika Salvi and Stewart, {James D.} and Thayer, {Julian F.} and Niek Verweij and Andrew Wong and Delilah Zabaneh and Zafarmand, {Mohammad H.} and Abdel Abdellaoui and Sulayma Albarwani and Christine Albert and Alvaro Alonso and Foram Ashar and Juha Auvinen and Tomas Axelsson and Baker, {Dewleen G.} and {De Bakker}, {Paul I.W.} and Matteo Barcella and Riad Bayoumi and Bieringa, {Rob J.} and Dorret Boomsma and Gabrielle Boucher and Britton, {Annie R.} and Christophersen, {Ingrid E.} and Andrea Dietrich and Ehret, {George B.} and Ellinor, {Patrick T.} and Markku Eskola and Felix, {Janine F.} and Floras, {John S.} and Franco, {Oscar H.} and Peter Friberg and Gademan, {Maaike G.J.} and Geyer, {Mark A.} and Vilmantas Giedraitis and Hartman, {Catharina A.} and Daiane Hemerich and Albert Hofman and Hottenga, {Jouke Jan} and Heikki Huikuri and Nina Hutri-K{\"a}h{\"o}nen and Xavier Jouven and Juhani Junttila and Markus Juonala and Kiviniemi, {Antti M.} and Kors, {Jan A.} and Meena Kumari and Tatiana Kuznetsova and Laurie, {Cathy C.} and Lefrandt, {Joop D.} and Yong Li and Yun Li and Duanping Liao and Limacher, {Marian C.} and Lin, {Henry J.} and Lindgren, {Cecilia M.} and Lubitz, {Steven A.} and Anubha Mahajan and Barbara McKnight and {Meyer Zu Schwabedissen}, Henriette and Yuri Milaneschi and Nina Mononen and Morris, {Andrew P.} and Nalls, {Mike A.} and Gerjan Navis and Melanie Neijts and Kjell Nikus and North, {Kari E.} and O'Connor, {Daniel T.} and Johan Ormel and Siegfried Perz and Annette Peters and Psaty, {Bruce M.} and Raitakari, {Olli T.} and Risbrough, {Victoria B.} and Sinner, {Moritz F.} and David Siscovick and Smit, {Johannes H.} and Smith, {Nicholas L.} and Soliman, {Elsayed Z.} and Nona Sotoodehnia and Staessen, {Jan A.} and Stein, {Phyllis K.} and Stilp, {Adrienne M.} and Katarzyna Stolarz-Skrzypek and Konstantin Strauch and Johan Sundstr{\"o}m and Swenne, {Cees A.} and Syv{\"a}nen, {Ann Christine} and Tardif, {Jean Claude} and Taylor, {Kent D.} and Alexander Teumer and Thornton, {Timothy A.} and Tinker, {Lesley E.} and Uitterlinden, {Andr{\'e} G.} and {Van Setten}, Jessica and Andreas Voss and Melanie Waldenberger and Wilhelmsen, {Kirk C.} and Gonneke Willemsen and Quenna Wong and Zhang, {Zhu Ming} and Zonderman, {Alan B.} and Daniele Cusi and Evans, {Michele K.} and Greiser, {Halina K.} and {Van Der Harst}, Pim and Mohammad Hassan and Erik Ingelsson and J{\"a}rvelin, {Marjo Riitta} and Stefan K{\"a}{\"a}b and Mika K{\"a}h{\"o}nen and Mika Kivimaki and Charles Kooperberg and Diana Kuh and Terho Lehtim{\"a}ki and Lars Lind and Nievergelt, {Caroline M.} and O'Donnell, {Chris J.} and Oldehinkel, {Albertine J.} and Brenda Penninx and Reiner, {Alexander P.} and Harri{\"e}tte Riese and {Van Roon}, {Arie M.} and Rioux, {John D.} and Rotter, {Jerome I.} and Tamar Sofer and Stricker, {Bruno H.} and Henning Tiemeier and Vrijkotte, {Tanja G.M.} and Asselbergs, {Folkert W.} and Brundel, {Bianca J.J.M.} and Heckbert, {Susan R.} and Whitsel, {Eric A.} and {Den Hoed}, Marcel and Harold Snieder and {De Geus}, {Eco J.C.}",

year = "2017",

month = jun,

day = "14",

doi = "10.1038/ncomms15805",

language = "English",

volume = "8",

journal = "Nature Communications",

issn = "2041-1723",

publisher = "Nature Publishing Group UK",

}

Nolte, IM, Munoz, ML, Tragante, V, Amare, AT, Jansen, R, Vaez, A, Von Der Heyde, B, Avery, CL, Bis, JC, Dierckx, B, Van Dongen, J, Gogarten, SM, Goyette, P, Hernesniemi, J, Huikari, V, Hwang, SJ, Jaju, D, Kerr, KF, Kluttig, A, Krijthe, BP, Kumar, J, Van Der Laan, SW, Lyytikäinen, LP, Maihofer, AX, Minassian, A, Van Der Most, PJ, Müller-Nurasyid, M, Nivard, M, Salvi, E, Stewart, JD, Thayer, JF, Verweij, N, Wong, A, Zabaneh, D, Zafarmand, MH, Abdellaoui, A, Albarwani, S, Albert, C, Alonso, A, Ashar, F, Auvinen, J, Axelsson, T, Baker, DG, De Bakker, PIW, Barcella, M, Bayoumi, R, Bieringa, RJ, Boomsma, D, Boucher, G, Britton, AR, Christophersen, IE, Dietrich, A, Ehret, GB, Ellinor, PT, Eskola, M, Felix, JF, Floras, JS, Franco, OH, Friberg, P, Gademan, MGJ, Geyer, MA, Giedraitis, V, Hartman, CA, Hemerich, D, Hofman, A, Hottenga, JJ, Huikuri, H, Hutri-Kähönen, N, Jouven, X, Junttila, J, Juonala, M, Kiviniemi, AM, Kors, JA, Kumari, M, Kuznetsova, T, Laurie, CC, Lefrandt, JD, Li, Y, Li, Y, Liao, D, Limacher, MC, Lin, HJ, Lindgren, CM, Lubitz, SA, Mahajan, A, McKnight, B, Meyer Zu Schwabedissen, H, Milaneschi, Y, Mononen, N, Morris, AP, Nalls, MA, Navis, G, Neijts, M, Nikus, K, North, KE, O'Connor, DT, Ormel, J, Perz, S, Peters, A, Psaty, BM, Raitakari, OT, Risbrough, VB, Sinner, MF, Siscovick, D, Smit, JH, Smith, NL, Soliman, EZ, Sotoodehnia, N, Staessen, JA, Stein, PK, Stilp, AM, Stolarz-Skrzypek, K, Strauch, K, Sundström, J, Swenne, CA, Syvänen, AC, Tardif, JC, Taylor, KD, Teumer, A, Thornton, TA, Tinker, LE, Uitterlinden, AG, Van Setten, J, Voss, A, Waldenberger, M, Wilhelmsen, KC, Willemsen, G, Wong, Q, Zhang, ZM, Zonderman, AB, Cusi, D, Evans, MK, Greiser, HK, Van Der Harst, P, Hassan, M, Ingelsson, E, Järvelin, MR, Kääb, S, Kähönen, M, Kivimaki, M, Kooperberg, C, Kuh, D, Lehtimäki, T, Lind, L, Nievergelt, CM, O'Donnell, CJ, Oldehinkel, AJ, Penninx, B, Reiner, AP, Riese, H, Van Roon, AM, Rioux, JD, Rotter, JI, Sofer, T, Stricker, BH, Tiemeier, H, Vrijkotte, TGM, Asselbergs, FW, Brundel, BJJM, Heckbert, SR, Whitsel, EA, Den Hoed, M, Snieder, H & De Geus, EJC 2017, 'Genetic loci associated with heart rate variability and their effects on cardiac disease risk', Nature Communications, vol. 8, 15805. https://doi.org/10.1038/ncomms15805

TY - JOUR

T1 - Genetic loci associated with heart rate variability and their effects on cardiac disease risk

AU - Nolte, Ilja M.

AU - Munoz, M. Loretto

AU - Tragante, Vinicius

AU - Amare, Azmeraw T.

AU - Jansen, Rick

AU - Vaez, Ahmad

AU - Von Der Heyde, Benedikt

AU - Avery, Christy L.

AU - Bis, Joshua C.

AU - Dierckx, Bram

AU - Van Dongen, Jenny

AU - Gogarten, Stephanie M.

AU - Goyette, Philippe

AU - Hernesniemi, Jussi

AU - Huikari, Ville

AU - Hwang, Shih Jen

AU - Jaju, Deepali

AU - Kerr, Kathleen F.

AU - Kluttig, Alexander

AU - Krijthe, Bouwe P.

AU - Kumar, Jitender

AU - Van Der Laan, Sander W.

AU - Lyytikäinen, Leo Pekka

AU - Maihofer, Adam X.

AU - Minassian, Arpi

AU - Van Der Most, Peter J.

AU - Müller-Nurasyid, Martina

AU - Nivard, Michel

AU - Salvi, Erika

AU - Stewart, James D.

AU - Thayer, Julian F.

AU - Verweij, Niek

AU - Wong, Andrew

AU - Zabaneh, Delilah

AU - Zafarmand, Mohammad H.

AU - Abdellaoui, Abdel

AU - Albarwani, Sulayma

AU - Albert, Christine

AU - Alonso, Alvaro

AU - Ashar, Foram

AU - Auvinen, Juha

AU - Axelsson, Tomas

AU - Baker, Dewleen G.

AU - De Bakker, Paul I.W.

AU - Barcella, Matteo

AU - Bayoumi, Riad

AU - Bieringa, Rob J.

AU - Boomsma, Dorret

AU - Boucher, Gabrielle

AU - Britton, Annie R.

AU - Christophersen, Ingrid E.

AU - Dietrich, Andrea

AU - Ehret, George B.

AU - Ellinor, Patrick T.

AU - Eskola, Markku

AU - Felix, Janine F.

AU - Floras, John S.

AU - Franco, Oscar H.

AU - Friberg, Peter

AU - Gademan, Maaike G.J.

AU - Geyer, Mark A.

AU - Giedraitis, Vilmantas

AU - Hartman, Catharina A.

AU - Hemerich, Daiane

AU - Hofman, Albert

AU - Hottenga, Jouke Jan

AU - Huikuri, Heikki

AU - Hutri-Kähönen, Nina

AU - Jouven, Xavier

AU - Junttila, Juhani

AU - Juonala, Markus

AU - Kiviniemi, Antti M.

AU - Kors, Jan A.

AU - Kumari, Meena

AU - Kuznetsova, Tatiana

AU - Laurie, Cathy C.

AU - Lefrandt, Joop D.

AU - Li, Yong

AU - Li, Yun

AU - Liao, Duanping

AU - Limacher, Marian C.

AU - Lin, Henry J.

AU - Lindgren, Cecilia M.

AU - Lubitz, Steven A.

AU - Mahajan, Anubha

AU - McKnight, Barbara

AU - Meyer Zu Schwabedissen, Henriette

AU - Milaneschi, Yuri

AU - Mononen, Nina

AU - Morris, Andrew P.

AU - Nalls, Mike A.

AU - Navis, Gerjan

AU - Neijts, Melanie

AU - Nikus, Kjell

AU - North, Kari E.

AU - O'Connor, Daniel T.

AU - Ormel, Johan

AU - Perz, Siegfried

AU - Peters, Annette

AU - Psaty, Bruce M.

AU - Raitakari, Olli T.

AU - Risbrough, Victoria B.

AU - Sinner, Moritz F.

AU - Siscovick, David

AU - Smit, Johannes H.

AU - Smith, Nicholas L.

AU - Soliman, Elsayed Z.

AU - Sotoodehnia, Nona

AU - Staessen, Jan A.

AU - Stein, Phyllis K.

AU - Stilp, Adrienne M.

AU - Stolarz-Skrzypek, Katarzyna

AU - Strauch, Konstantin

AU - Sundström, Johan

AU - Swenne, Cees A.

AU - Syvänen, Ann Christine

AU - Tardif, Jean Claude

AU - Taylor, Kent D.

AU - Teumer, Alexander

AU - Thornton, Timothy A.

AU - Tinker, Lesley E.

AU - Uitterlinden, André G.

AU - Van Setten, Jessica

AU - Voss, Andreas

AU - Waldenberger, Melanie

AU - Wilhelmsen, Kirk C.

AU - Willemsen, Gonneke

AU - Wong, Quenna

AU - Zhang, Zhu Ming

AU - Zonderman, Alan B.

AU - Cusi, Daniele

AU - Evans, Michele K.

AU - Greiser, Halina K.

AU - Van Der Harst, Pim

AU - Hassan, Mohammad

AU - Ingelsson, Erik

AU - Järvelin, Marjo Riitta

AU - Kääb, Stefan

AU - Kähönen, Mika

AU - Kivimaki, Mika

AU - Kooperberg, Charles

AU - Kuh, Diana

AU - Lehtimäki, Terho

AU - Lind, Lars

AU - Nievergelt, Caroline M.

AU - O'Donnell, Chris J.

AU - Oldehinkel, Albertine J.

AU - Penninx, Brenda

AU - Reiner, Alexander P.

AU - Riese, Harriëtte

AU - Van Roon, Arie M.

AU - Rioux, John D.

AU - Rotter, Jerome I.

AU - Sofer, Tamar

AU - Stricker, Bruno H.

AU - Tiemeier, Henning

AU - Vrijkotte, Tanja G.M.

AU - Asselbergs, Folkert W.

AU - Brundel, Bianca J.J.M.

AU - Heckbert, Susan R.

AU - Whitsel, Eric A.

AU - Den Hoed, Marcel

AU - Snieder, Harold

AU - De Geus, Eco J.C.

PY - 2017/6/14

Y1 - 2017/6/14

N2 - Reduced cardiac vagal control reflected in low heart rate variability (HRV) is associated with greater risks for cardiac morbidity and mortality. In two-stage meta-analyses of genome-wide association studies for three HRV traits in up to 53,174 individuals of European ancestry, we detect 17 genome-wide significant SNPs in eight loci. HRV SNPs tag non-synonymous SNPs (in NDUFA11 and KIAA1755), expression quantitative trait loci (eQTLs) (influencing GNG11, RGS6 and NEO1), or are located in genes preferentially expressed in the sinoatrial node (GNG11, RGS6 and HCN4). Genetic risk scores account for 0.9 to 2.6% of the HRV variance. Significant genetic correlation is found for HRV with heart rate (-0.74

AB - Reduced cardiac vagal control reflected in low heart rate variability (HRV) is associated with greater risks for cardiac morbidity and mortality. In two-stage meta-analyses of genome-wide association studies for three HRV traits in up to 53,174 individuals of European ancestry, we detect 17 genome-wide significant SNPs in eight loci. HRV SNPs tag non-synonymous SNPs (in NDUFA11 and KIAA1755), expression quantitative trait loci (eQTLs) (influencing GNG11, RGS6 and NEO1), or are located in genes preferentially expressed in the sinoatrial node (GNG11, RGS6 and HCN4). Genetic risk scores account for 0.9 to 2.6% of the HRV variance. Significant genetic correlation is found for HRV with heart rate (-0.74

UR - http://www.scopus.com/inward/record.url?scp=85020487334&partnerID=8YFLogxK

U2 - 10.1038/ncomms15805

DO - 10.1038/ncomms15805

M3 - Article

C2 - 28613276

AN - SCOPUS:85020487334

VL - 8

JO - Nature Communications

JF - Nature Communications

SN - 2041-1723

M1 - 15805

ER -

Genetic loci associated with heart rate variability and their effects on cardiac disease risk

Abstract

Access to Document

Other files and links

Cite this