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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.; [...]

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

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  • Media type: E-Article
  • Title: Genetic loci associated with heart rate variability and their effects on cardiac disease risk
  • Contributor: 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.; [...]
  • imprint: Springer Science and Business Media LLC, 2017
  • Published in: Nature Communications
  • Language: English
  • DOI: 10.1038/ncomms15805
  • ISSN: 2041-1723
  • Origination:
  • Footnote:
  • Description: <jats:title>Abstract</jats:title><jats:p>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 <jats:italic>NDUFA11</jats:italic> and <jats:italic>KIAA1755</jats:italic>), expression quantitative trait loci (eQTLs) (influencing <jats:italic>GNG11</jats:italic>, <jats:italic>RGS6</jats:italic> and <jats:italic>NEO1</jats:italic>), or are located in genes preferentially expressed in the sinoatrial node (<jats:italic>GNG11</jats:italic>, <jats:italic>RGS6</jats:italic> and <jats:italic>HCN4)</jats:italic>. 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&lt;<jats:italic>r</jats:italic><jats:sub><jats:italic>g</jats:italic></jats:sub>&lt;−0.55) and blood pressure (−0.35&lt;<jats:italic>r</jats:italic><jats:sub><jats:italic>g</jats:italic></jats:sub>&lt;−0.20). These findings provide clinically relevant biological insight into heritable variation in vagal heart rhythm regulation, with a key role for genetic variants (<jats:italic>GNG11</jats:italic>, <jats:italic>RGS6)</jats:italic> that influence G-protein heterotrimer action in GIRK-channel induced pacemaker membrane hyperpolarization.</jats:p>
  • Access State: Open Access