Heritability and the Genetic Correlation of Heart Rate Variability and Blood Pressure in >29 000 Families

Abstract

Dysregulation of the cardiac autonomic nervous system, as indexed by reduced heart rate variability (HRV), has been associated with the development of high blood pressure (BP). However, the underlying pathological mechanisms are not yet fully understood. This study aimed to estimate heritability of HRV and BP and to determine their genetic overlap. We used baseline data of the 3-generation Lifelines population-based cohort study (n=149 067; mean age, 44.5). In-house software was used to calculate root mean square of successive differences and SD of normal-to-normal intervals as indices of HRV based on 10-second resting ECGs. BP was recorded with an automatic BP monitor. We estimated heritabilities and genetic correlations with variance components methods in ASReml software. We additionally estimated genetic correlations with bivariate linkage disequilibrium score regression using publicly available genome-wide association study data. The heritability (SE) estimates were 15.6% (0.90%) for SD of normal-to-normal intervals and 17.9% (0.90%) for root mean square of successive differences. For BP measures, they ranged from 24.4% (0.90%) for pulse pressure to 30.3% (0.90%) for diastolic BP. Significant negative genetic correlations (all P <0.0001) of root mean square of successive differences/SD of normal-to-normal intervals with systolic BP (−0.20/−0.16) and with diastolic BP (−0.15/−0.13) were observed. LD score regression showed largely consistent genetic correlation estimates of root mean square of successive differences/SD of normal-to-normal intervals with systolic BP (range, −0.08 to −0.23) and diastolic BP (range, −0.20 to −0.27). Our study shows a substantial contribution of genetic factors in explaining the variance of HRV and BP measures in the general population. The significant negative genetic correlations between HRV and BP indicate that genetic pathways for HRV and BP partially overlap.

A genome-wide association study identifies a novel association between SDC3 and apparent treatment-resistant hypertension

“…This study represents the first GWAS of aTRH in the Chinese Han population. Over the past few years, GWAS and exome sequencing studies have resulted in an unparalleled burst of discovery in the genetics of blood pressure regulation and hypertension [18][19][20][21]. More importantly, GWAS, while expanding the list of common genetic variants associated with blood pressure and hypertension, are also uncovering novel pathways of blood pressure regulation that augur a new era of novel drug development, repurposing, and stratification in the management of hypertension [18].…”

Device-evaluated autonomic nervous function for predicting ventricular arrhythmias and all-cause mortality in patients who underwent cardiac resynchronization therapy-defibrillator

“…The improvement of ANS function promoted by exercise may also be an indirect reason for the improvement in prognosis by regular exercise ( Cheng et al, 2022 ). However, hypertension and ischemic heart disease were also considered to be associated with baseline ANS function in the general population ( Weiss et al, 1991 ; Tegegne et al, 2020 ), but they did not play decisive roles in postoperative HRV for HF patients with CRT-D. Nevertheless, the recovery of ANS function in patients with diabetes needs to be further explored, it is clear that the ANS function of these patients deserves further attention, and improving daily activities may help to benefit more from CRT-D.…”

Influence of family history of hypertension on blood pressure and heart rate variability in young adults: a meta-analysis

“…Additional studies have reported impaired parasympathetic drive present in normotensive subjects with FHH + [53] and HRV indices associated with the incidence of hypertension over 3 years [54]. Although BP and HRV concordance within families can be attributed to genetic susceptibility and shared environmental exposures, a large family study [55] showed that the contribution of genetic factors to the variance of diastolic BP (24.4%), RMSSD (17.9%), and SDNN (15.6%) in the general population is substantial, and the genes for BP and HRV partially overlap. However, the autonomic dysfunctions are not necessarily accompanied by increased BP in young adults [14–17,27].…”