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

Article scientifique 2017 Anglais

Résumé

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.

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Nolte, I., Muñoz, M., Tragante, V., Amare, A., Jansen, R., Vaez, A., Heyde, B., Avery, C., Bis, J., Dierckx, B., Dongen, J., Gogarten, S., Goyette, P., Hernesniemi, J., Huikari, V., Hwang, S., Jaju, D., Kerr, K., Kluttig, A., Krijthe, B., Kumar, J., Laan, S., Lyytikäinen, L., Maihofer, A., Minassian, A., Most, P., Müller‐Nurasyid, M., Nivard, M., Salvi, E., Stewart, J., Thayer, J., Verweij, N., Wong, A., Zabaneh, D., Zafarmand, M., Abdellaoui, A., Albarwani, S., Albert, C., Alonso, Á., Ashar, F., Auvinen, J., Axelsson, T., Baker, D., Bakker, P., Barcella, M., Bayoumi, R., Bieringa, R., Boomsma, D., Boucher, G., Britton, A., Christophersen, I., Dietrich, A., Ehret, G., Ellinor, P., Eskola, M., Felix, J., Floras, J., Franco, O., Friberg, P., Gademan, M., Geyer, M., Giedraitis, V., Hartman, C., Hemerich, D., Hofman, A., Hottenga, J., Huikuri, H., Hutri‐Kähönen, N., Jouven, X., Junttila, J., Juonala, M., Kiviniemi, A., Kors, J., Kumari, M., Kuznetsova, T., Laurie, C., Lefrandt, J., Li, Y., Li, Y., Liao, D., Limacher, M., Lin, H., Lindgren, C., Lubitz, S., Mahajan, A., McKnight, B., Schwabedissen, H., Milaneschi, Y., Mononen, N., Morris, A., Nalls, M., Navis, G., Neijts, M., Nikus, K., North, K., O’Connor, D., Ormel, J., Perz, S., Peters, A., Psaty, B. (2017). Genetic loci associated with heart rate variability and their effects on cardiac disease risk. https://doi.org/10.1038/ncomms15805

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Auteur(s)

Ilja M. Nolte M. Loretto Muñoz 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 G. Nivard Erika Salvi James D. Stewart Julian F. Thayer Niek Verweij Andrew Wong Delilah Zabaneh Mohammad Hadi Zafarmand Abdel Abdellaoui Sulayma Albarwani Christine M. Albert Álvaro Alonso Foram N. Ashar Juha Auvinen Tomas Axelsson Dewleen G. Baker Paul I. W. de Bakker Matteo Barcella Riad Bayoumi Rob J. Bieringa Dorret I. Boomsma Gabrielle Boucher Annie Britton Ingrid E. Christophersen Andrea Dietrich G. 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 V. 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 E. 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

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