Phenotypic but not genetically predicted heart rate variability associated with all-cause mortality

Area of Science:

• Genetics
• Cardiology
• Molecular Biology

Background:

• Low heart rate variability (HRV) is a known predictor of increased mortality.
• The underlying molecular mechanisms connecting HRV and mortality remain poorly understood.

Purpose of the Study:

• To identify novel genetic loci associated with HRV.
• To assess the association of phenotypic HRV and genetically predicted HRV with mortality.

Main Methods:

• Genome-wide association study (GWAS) in 46,075 European ancestry individuals from the UK Biobank.
• Identification of genetic variants associated with HRV traits.
• Prospective analysis of phenotypic HRV and genetically predicted HRV (using genetic risk scores) in relation to mortality.

Main Results:

• Identified 17 independent genome-wide significant genetic variants in 16 loci associated with HRV traits.
• Eight novel loci (RNF220, GNB4, LINCR-002, KLHL3/HNRNPA0, CHRM2, KCNJ5, MED13L, and C160rf72) were reported for the first time.
• Lower phenotypic HRV was associated with a higher risk of all-cause mortality.
• Genetically predicted HRV was not associated with mortality.

Conclusions:

• The study provides novel biological insights into the mechanisms underlying HRV.
• Findings highlight the role of the cardiac autonomic nervous system, as indexed by HRV, in predicting mortality.