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

  • Author(s): 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
  • et al.

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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