Genetic loci associated with heart rate variability and their effects on cardiac disease risk
Minassian A; Thayer JF; Boomsma D; Kumari M; Nolte IM; van der Harst P; Riese H; Christophersen IE; Teumer A; Sotoodehnia N; Maihofer AX; Avery CL; Kahonen M; Staessen JA; Rioux JD; Voss A; Kluttig A; Morris AP; Sundstrom J; Vaez A; Huikuri H; zu Schwabedissen HM; Lindgren CM; Zonderman AB; Huikari V; Wilhelmsen KC; Reiner AP; Albarwani S; North KE; Stilp AM; Bis JC; Nivard M; Wong A; Navis G; Stolarz-Skrzypek K; Ellinor PT; Zhang ZM; McKnight B; Whitsel EA; Albert C; Giedraitis V; Heckbert SR; Baker DG; Neijts M; Stein PK; Jansen R; Milaneschi Y; Hwang SJ; Liao DP; Perz S; Geyer MA; Li Y; van Roon AM; Rotter JI; Boucher G; Ormel J; Zafarmand MH; O'Connor DT; van der Most PJ; Verweij N; de Bakker PIW; Friberg P; Hutri-Kahonen N; Axelsson T; Cusi D; Amare AT; Soliman EZ; Asselbergs FW; Abdellaoui A; Britton AR; Salvi E; Gogarten SM; Penninx B; Hassan M; Mahajan A; Lind L; Nikus K; Smith NL; Lyytikainen LP; Kiviniemi AM; Greiser HK; Wong QN; Kooperberg C; van Dongen J; Lin HJ; Uitterlinden AG; Kivimaki M; Jarvelin MR; Kuznetsova T; Sofer T; Syvanen AC; Evans MK; Sinner MF; Nievergelt CM; O'Donnell CJ; Siscovick D; von der Heyde B; Psaty BM; Lubitz SA; Smit JH; Munoz ML; Hofman A; Floras JS; Franco OH; Stricker BH; Gademan MGJ; Bieringa RJ; de Geus EJC; Taylor KD; Hemerich D; Snieder H; Dietrich A; Barcella M; Kaab S; van Setten J; Brundel BJJM; Ingelsson E; Jaju D; Stewart JD; Strauch K; Kerr KF; Tiemeier H; Vrijkotte TGM; Willemsen G; Laurie CC; van der Laan SW; Hartman CA; Tragante V; Goyette P; Swenne CA; Hottenga JJ; Thornton TA; Risbrough VB; Oldehinkel AJ; Felix JF; Tardif JC; Kumar J; Mononen N; Zabaneh D; Muller-Nurasyid M; Ashar F; Limacher MC; Eskola M; Peters A; Lefrandt JD; Ehret GB; den Hoed M; Juonala M; Lehtimaki T; Hernesniemi J; Alonso A; Dierckx B; Auvinen J; Nalls MA; Raitakari OT; Kuh D; Kors JA; Krijthe BP; Bayoumi R; Waldenberger M; Tinker LE
Genetic loci associated with heart rate variability and their effects on cardiac disease risk
NATURE PUBLISHING GROUP
Julkaisun pysyvä osoite on:
https://urn.fi/URN:NBN:fi-fe2021042717106
https://urn.fi/URN:NBN:fi-fe2021042717106
Tiivistelmä
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.
Kokoelmat
- Rinnakkaistallenteet [19207]