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e-Article

Genetic loci associated with heart rate variability and their effects on cardiac disease risk.
Document Type
article
Author
Nolte, Ilja MMunoz, M LorettoTragante, ViniciusAmare, Azmeraw TJansen, RickVaez, Ahmadvon der Heyde, BenediktAvery, Christy LBis, Joshua CDierckx, Bramvan Dongen, JennyGogarten, Stephanie MGoyette, PhilippeHernesniemi, JussiHuikari, VilleHwang, Shih-JenJaju, DeepaliKerr, Kathleen FKluttig, AlexanderKrijthe, Bouwe PKumar, Jitendervan der Laan, Sander WLyytikäinen, Leo-PekkaMaihofer, Adam XMinassian, Arpivan der Most, Peter JMüller-Nurasyid, MartinaNivard, MichelSalvi, ErikaStewart, James DThayer, Julian FVerweij, NiekWong, AndrewZabaneh, DelilahZafarmand, Mohammad HAbdellaoui, AbdelAlbarwani, SulaymaAlbert, ChristineAlonso, AlvaroAshar, ForamAuvinen, JuhaAxelsson, TomasBaker, Dewleen Gde Bakker, Paul IWBarcella, MatteoBayoumi, RiadBieringa, Rob JBoomsma, DorretBoucher, GabrielleBritton, Annie RChristophersen, IngridDietrich, AndreaEhret, George BEllinor, Patrick TEskola, MarkkuFelix, Janine FFloras, John SFranco, Oscar HFriberg, PeterGademan, Maaike GJGeyer, Mark AGiedraitis, VilmantasHartman, Catharina AHemerich, DaianeHofman, AlbertHottenga, Jouke-JanHuikuri, HeikkiHutri-Kähönen, NinaJouven, XavierJunttila, JuhaniJuonala, MarkusKiviniemi, Antti MKors, Jan AKumari, MeenaKuznetsova, TatianaLaurie, Cathy CLefrandt, Joop DLi, YongLi, YunLiao, DuanpingLimacher, Marian CLin, Henry JLindgren, Cecilia MLubitz, Steven AMahajan, AnubhaMcKnight, BarbaraZu Schwabedissen, Henriette MeyerMilaneschi, YuriMononen, NinaMorris, Andrew PNalls, Mike ANavis, GerjanNeijts, MelanieNikus, KjellNorth, Kari EO'Connor, Daniel TOrmel, JohanPerz, SiegfriedPeters, AnnettePsaty, Bruce M
Source
Nature communications. 8(1)
Subject
Humans
Heart Diseases
Genetic Predisposition to Disease
RGS Proteins
Potassium Channels
Muscle Proteins
Risk Factors
Cohort Studies
Blood Pressure
Heart Rate
Polymorphism
Single Nucleotide
Quantitative Trait Loci
European Continental Ancestry Group
Genome-Wide Association Study
Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels
Cardiovascular
Genetics
Heart Disease
Language
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 (-0.74g