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

Authors :
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.
Lyytikainen, Leo-Pekka
Maihofer, Adam X.
Minassian, Arpi
van der Most, Peter J.
Mueller-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 E.
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-Kahonen, 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
Sundstrom, Johan
Swenne, Cees A.
Syvänen, Ann-Christine
Tardif, Jean-Claude
Taylor, Kent D.
Teumer, Alexander
Thornton, Timothy A.
Tinker, Lesley E.
Uitterlinden, Andre 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
Jarvelin, Marjo-Riitta
Kaab, Stefan
Kahonen, Mika
Kivimaki, Mika
Kooperberg, Charles
Kuh, Diana
Lehtimaki, Terho
Lind, Lars
Nievergelt, Caroline M.
O'Donnell, Chris J.
Oldehinkel, Albertine J.
Penninx, Brenda
Reiner, Alexander P.
Riese, Harriette
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.
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.
Lyytikainen, Leo-Pekka
Maihofer, Adam X.
Minassian, Arpi
van der Most, Peter J.
Mueller-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 E.
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-Kahonen, 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
Sundstrom, Johan
Swenne, Cees A.
Syvänen, Ann-Christine
Tardif, Jean-Claude
Taylor, Kent D.
Teumer, Alexander
Thornton, Timothy A.
Tinker, Lesley E.
Uitterlinden, Andre 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
Jarvelin, Marjo-Riitta
Kaab, Stefan
Kahonen, Mika
Kivimaki, Mika
Kooperberg, Charles
Kuh, Diana
Lehtimaki, Terho
Lind, Lars
Nievergelt, Caroline M.
O'Donnell, Chris J.
Oldehinkel, Albertine J.
Penninx, Brenda
Reiner, Alexander P.
Riese, Harriette
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.
Publication Year :
2017

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.

Details

Database :
OAIster
Notes :
application/pdf, English
Publication Type :
Electronic Resource
Accession number :
edsoai.on1234033535
Document Type :
Electronic Resource
Full Text :
https://doi.org/10.1038.ncomms15805