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 & 144 others 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 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

Research output: Contribution to journalArticle

20 Citations (Scopus)

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<rg<-0.55) and blood pressure (-0.35<rg<-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.

LanguageEnglish
Pages15805
JournalNature Communications
Volume8
DOIs
Publication statusPublished - 14 Jun 2017
Externally publishedYes

Keywords

  • Journal Article

Cite this

Nolte, Ilja M ; Munoz, M Loretto ; Tragante, Vinicius ; Amare, Azmeraw T ; Jansen, Rick ; Vaez, Ahmad ; von der Heyde, Benedikt ; Avery, Christy L ; Bis, Joshua C ; Dierckx, Bram ; van Dongen, Jenny ; Gogarten, Stephanie M ; Goyette, Philippe ; Hernesniemi, Jussi ; Huikari, Ville ; Hwang, Shih-Jen ; Jaju, Deepali ; Kerr, Kathleen F ; Kluttig, Alexander ; Krijthe, Bouwe P ; Kumar, Jitender ; van der Laan, Sander W ; Lyytikäinen, Leo-Pekka ; Maihofer, Adam X ; Minassian, Arpi ; van der Most, Peter J ; Müller-Nurasyid, Martina ; Nivard, Michel ; Salvi, Erika ; Stewart, James D ; Thayer, Julian F ; Verweij, Niek ; Wong, Andrew ; Zabaneh, Delilah ; Zafarmand, Mohammad H ; Abdellaoui, Abdel ; Albarwani, Sulayma ; Albert, Christine ; Alonso, Alvaro ; Ashar, Foram ; Auvinen, Juha ; Axelsson, Tomas ; Baker, Dewleen G ; de Bakker, Paul I W ; Barcella, Matteo ; Bayoumi, Riad ; Bieringa, Rob J ; Boomsma, Dorret ; Boucher, Gabrielle ; Britton, Annie R ; Christophersen, Ingrid ; Dietrich, Andrea ; Ehret, George B ; Ellinor, Patrick T ; Eskola, Markku ; Felix, Janine F ; Floras, John S ; Franco, Oscar H ; Friberg, Peter ; Gademan, Maaike G J ; Geyer, Mark A ; Giedraitis, Vilmantas ; Hartman, Catharina A ; Hemerich, Daiane ; Hofman, Albert ; Hottenga, Jouke-Jan ; Huikuri, Heikki ; Hutri-Kähönen, Nina ; Jouven, Xavier ; Junttila, Juhani ; Juonala, Markus ; Kiviniemi, Antti M ; Kors, Jan A ; Kumari, Meena ; Kuznetsova, Tatiana ; Laurie, Cathy C ; Lefrandt, Joop D ; Li, Yong ; Li, Yun ; Liao, Duanping ; Limacher, Marian C ; Lin, Henry J ; Lindgren, Cecilia M ; Lubitz, Steven A ; Mahajan, Anubha ; McKnight, Barbara ; Zu Schwabedissen, Henriette Meyer ; Milaneschi, Yuri ; Mononen, Nina ; Morris, Andrew P ; Nalls, Mike A ; Navis, Gerjan ; Neijts, Melanie ; Nikus, Kjell ; North, Kari E ; O'Connor, Daniel T ; Ormel, Johan ; Perz, Siegfried ; Peters, Annette ; Psaty, Bruce M ; Raitakari, Olli T ; Risbrough, Victoria B ; Sinner, Moritz F ; Siscovick, David ; Smit, Johannes H ; Smith, Nicholas L ; Soliman, Elsayed Z ; Sotoodehnia, Nona ; Staessen, Jan A ; Stein, Phyllis K ; Stilp, Adrienne M ; Stolarz-Skrzypek, Katarzyna ; Strauch, Konstantin ; Sundström, Johan ; Swenne, Cees A ; Syvänen, Ann-Christine ; Tardif, Jean-Claude ; Taylor, Kent D ; Teumer, Alexander ; Thornton, Timothy A ; Tinker, Lesley E ; Uitterlinden, André G ; van Setten, Jessica ; Voss, Andreas ; Waldenberger, Melanie ; Wilhelmsen, Kirk C ; Willemsen, Gonneke ; Wong, Quenna ; Zhang, Zhu-Ming ; Zonderman, Alan B ; Cusi, Daniele ; Evans, Michele K ; Greiser, Halina K ; van der Harst, Pim ; Hassan, Mohammad ; Ingelsson, Erik ; Järvelin, Marjo-Riitta ; Kääb, Stefan ; Kähönen, Mika ; Kivimaki, Mika ; Kooperberg, Charles ; Kuh, Diana ; Lehtimäki, Terho ; Lind, Lars ; Nievergelt, Caroline M ; O'Donnell, Chris J ; Oldehinkel, Albertine J ; Penninx, Brenda ; Reiner, Alexander P ; Riese, Harriëtte ; van Roon, Arie M ; Rioux, John D ; Rotter, Jerome I ; Sofer, Tamar ; Stricker, Bruno H ; Tiemeier, Henning ; Vrijkotte, Tanja G M ; Asselbergs, Folkert W ; Brundel, Bianca J J M ; Heckbert, Susan R ; Whitsel, Eric A ; den Hoed, Marcel ; Snieder, Harold ; de Geus, Eco J C. / Genetic loci associated with heart rate variability and their effects on cardiac disease risk. In: Nature Communications. 2017 ; Vol. 8. pp. 15805.
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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",
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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, S-J, Jaju, D, Kerr, KF, Kluttig, A, Krijthe, BP, Kumar, J, van der Laan, SW, Lyytikäinen, L-P, 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, I, 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, J-J, 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, Zu Schwabedissen, HM, 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, A-C, Tardif, J-C, Taylor, KD, Teumer, A, Thornton, TA, Tinker, LE, Uitterlinden, AG, van Setten, J, Voss, A, Waldenberger, M, Wilhelmsen, KC, Willemsen, G, Wong, Q, Zhang, Z-M, Zonderman, AB, Cusi, D, Evans, MK, Greiser, HK, van der Harst, P, Hassan, M, Ingelsson, E, Järvelin, M-R, 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, pp. 15805. https://doi.org/10.1038/ncomms15805

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

In: Nature Communications, Vol. 8, 14.06.2017, p. 15805.

Research output: Contribution to journalArticle

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

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 - Zu Schwabedissen, Henriette Meyer

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

KW - Journal Article

U2 - 10.1038/ncomms15805

DO - 10.1038/ncomms15805

M3 - Article

VL - 8

SP - 15805

JO - Nature Communications

T2 - Nature Communications

JF - Nature Communications

SN - 2041-1723

ER -