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

Nat Commun
Authors
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 (-0.74-0.55) and blood pressure (-0.35-0.20). 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.

Year of Publication
2017
Journal
Nat Commun
Volume
8
Pages
15805
Date Published
2017 Jun 14
ISSN
2041-1723
DOI
10.1038/ncomms15805
PubMed ID
28613276
PubMed Central ID
PMC5474732
Links
Grant list
R01 HL120393 / HL / NHLBI NIH HHS / United States
U01 HL130114 / HL / NHLBI NIH HHS / United States
P01 GM099568 / GM / NIGMS NIH HHS / United States
MC_UU_12019/1 / Medical Research Council / United Kingdom
UL1 TR000124 / TR / NCATS NIH HHS / United States
R01 HL105756 / HL / NHLBI NIH HHS / United States
P30 DK063491 / DK / NIDDK NIH HHS / United States
I01 BX002558 / BX / BLRD VA / United States
S10 OD020069 / OD / NIH HHS / United States
P2C HD050924 / HD / NICHD NIH HHS / United States
K23 HL114724 / HL / NHLBI NIH HHS / United States
R01 HL116747 / HL / NHLBI NIH HHS / United States