Heritability of Heart Rate Response to Arousals in Twins

Abstract

Objectives: To determine if the large and highly reproducible interindividual differences in arousal intensity and heart rate response to arousal (ΔHR) during non-REM sleep are heritable.

Methods: Polysomnograms of 55 monozygotic (14 male and 41 female pairs) and 36 dizygotic (15 male and 21 female pairs) same-sex twin pairs were analyzed. Arousals were scored using the 2012 American Academy of Sleep Medicine criteria. Arousal intensity was scaled (between 0 and 9) using an automatic algorithm based on the change in electroencephalogram time and frequency characteristics. The ΔHR was determined at each arousal. We calculated average arousal duration, average arousal intensity, average overall ΔHR, average ΔHR at a given arousal intensity, slope of ΔHR per arousal intensity, and arousal intensity threshold of ΔHR.

Results: The intraclass correlations among monozygotic and dizygotic twin pairs were 0.663 and 0.146, respectively, for average arousal intensity, and 0.449 and 0, respectively, for arousal intensity threshold of ΔHR controlling for age, sex, and race. These values imply large broad sense heritability (H2) for these traits. This evidence was confirmed by a robust maximum likelihood-based variance components estimation approach, with an additive genetic heritability of 0.64 (95% confidence interval: 0.48 to 0.80) for average arousal intensity and a combined additive and dominance genetic heritability and of 0.46 (0.25 to 0.68) for arousal intensity threshold of ΔHR. Results also suggested significant additive genetic effects for average arousal duration, ΔHR at arousal intensity scale 4 and the overall average ΔHR.

Conclusion: Genetic factors explain a significant fraction of the phenotypic variability for average arousal intensity and arousal intensity threshold of ΔHR. Results suggest that the duration of arousals and specific average ΔHR values may also be heritable traits.

Clinical trial registration: NCT02827461.

Keywords: dizygotic; monozygotic; polysomnogram.

© Sleep Research Society 2017. Published by Oxford University Press on behalf of the Sleep Research Society. All rights reserved. For permissions, please e-mail journals.permissions@oup.com.

Figures

Figure 1

Examples of arousals with different scales in the same subject. EMG, chin electromyogram; C3/M2 and C4/M1 are electroencephalograms; EKG, electrocardiogram. Numbers above the electrocardiogram represent instantaneous heart rate. Arousal scale is highly sensitive to beta power (as in the lower two panels).

Figure 2

Change in heart rate with the arousal (ΔHR) at different arousal intensities in a representative subject. Each solid dot is the ΔHR with each arousal and each open dot is the average ΔHR at a given arousal intensity. The equation of best-fitted regression line to the average HR responses is y = 2.6x − 2.6. The arousal intensity threshold for ΔHR is 1.0.

Figure 3

Schematic representation of the impact of slope and intercept on ΔHR at specific arousal intensities. (A) A shift in intercept when slope is relatively low. (B) the same shift in intercept when slope is high. ΔHRT, contribution of shift in intercept to ΔHR; ΔHRS, contribution of slope to ΔHR. Note that the contribution of threshold shift (T) to ΔHR (i.e. ΔHRT + ΔHRS) progressively decreases as arousal intensity increases regardless of slope.