Heritability of performance deficit accumulation during acute sleep deprivation in twins

Abstract

Study objectives: To determine if the large and highly reproducible interindividual differences in rates of performance deficit accumulation during sleep deprivation, as determined by the number of lapses on a sustained reaction time test, the Psychomotor Vigilance Task (PVT), arise from a heritable trait.

Design: Prospective, observational cohort study.

Setting: Academic medical center.

Participants: There were 59 monozygotic (mean age 29.2 ± 6.8 [SD] yr; 15 male and 44 female pairs) and 41 dizygotic (mean age 26.6 ± 7.6 yr; 15 male and 26 female pairs) same-sex twin pairs with a normal polysomnogram.

Interventions: Thirty-eight hr of monitored, continuous sleep deprivation.

Measurements and results: Patients performed the 10-min PVT every 2 hr during the sleep deprivation protocol. The primary outcome was change from baseline in square root transformed total lapses (response time ≥ 500 ms) per trial. Patient-specific linear rates of performance deficit accumulation were separated from circadian effects using multiple linear regression. Using the classic approach to assess heritability, the intraclass correlation coefficients for accumulating deficits resulted in a broad sense heritability (h(2)) estimate of 0.834. The mean within-pair and among-pair heritability estimates determined by analysis of variance-based methods was 0.715. When variance components of mixed-effect multilevel models were estimated by maximum likelihood estimation and used to determine the proportions of phenotypic variance explained by genetic and nongenetic factors, 51.1% (standard error = 8.4%, P < 0.0001) of twin variance was attributed to combined additive and dominance genetic effects.

Conclusion: Genetic factors explain a large fraction of interindividual variance among rates of performance deficit accumulations on PVT during sleep deprivation.

Keywords: Sleep homeostasis; sleep deprivation; twins.

Figure 1

Mean ± standard deviation change in transformed Psychomotor Vigilance Task (PVT) lapses on the trials performed every 2 hr during the 38-hr sleep deprivation period in the monozygotic (MZ, open diamond) and dizygotic (DZ, closed circle) twin pairs. Results on the 1st trial at 2 hr were used as the reference. See text for details.

Figure 2

The individual linear slopes of the change in Psychomotor Vigilance Task (PVT) transformed lapses during the sleep deprivation period in the monozygotic (MZ, left panel) and dizygotic (DZ, right panel) twin pairs. Data for each MZ and DZ twin pair are plotted together on the abscissa. In each panel, the pairs are ordered by the magnitude of their impairment (averaged over each pair), with the most resistant twin pair on the left and the most vulnerable twin pair on the right. The panels reveal substantial differences in individual responses to sleep deprivation. As is visually apparent, the intraclass correlation revealed greater similarity within MZ twin pairs than within DZ twin pairs. There was 56.2% of the total variance in the MZ twins that was due to variance between pairs whereas only 14.5% of the total variance in DZ twins was due to variance between pairs. ICC, intraclass correlation.

Figure 3

Mean ± SD change in transformed Psychomotor Vigilance Task (PVT) lapses on the trials performed every 2 hr during the 38-hr sleep deprivation period by PER3 genotype (5/5, 4/5, and 4/4). Results on the first trial at 2-hr were used as the reference. GT, genotype. See text for details.

Figure 4

Mean ± standard deviation change in transformed PVT lapses during specific time periods by PER3 genotype (5/5, 4/5, and 4/4).