"No thanks, it keeps me awake": the genetics of coffee-attributed sleep disturbance

Abstract

Study objectives: Previous genetic investigations of sleep disturbance have shown various measures of sleep quality and sleep pattern to be heritable. But none of these studies have investigated the genetic predisposition to sleep disturbance attributed to caffeine. In this study, the heritability of coffee-attributed sleep disturbance and its relationship with other sleep measures were estimated, and chromosomal regions influencing this trait were identified.

Design: A classical twin design was used to estimate the heritability of coffee-attributed sleep disturbance and its genetic covariance with other measures of sleep disturbance (e.g., due to anxiety, depression) and sleep quality (e.g., variability in sleep quality). To locate quantitative trait loci influencing coffee-attributed sleep disturbance, a genome-wide linkage screen of 1395 microsatellite markers was performed.

Participants: The study included 3808 Australian adult twin pairs (n = 1799 monozygous pairs; n = 2009 dizygous pairs). A subsample of 1989 individuals from 1175 families was used for the linkage analysis.

Measurements and results: The heritability of coffee-attributed sleep disturbance (measured by self report) was approximately 0.40, with three fourths of this genetic variance explained by genes unrelated to the general sleep disturbance factor. One region of significant linkage to coffee-attributed sleep disturbance was identified on chromosome 2q (LOD score of 2.9).

Conclusions: Although no candidate genes known to be related to caffeine metabolism or sleep disorder were identified in the significant linkage region, 2 candidates were found under a smaller peak on chromosome 17q.

Figure 1

Path diagram representing the additive genetic (A) and common environmental (C) factor structure of the covariance between sleep disturbance measures in women.

Figure 2

Path diagram representing the additive genetic (A) and common environmental (C) factor structure of the covariance between sleep disturbance measures in men

Figure 3

Linkage plot depicting chromosomal regions across the genome that are related to coffee-attributed insomnia. Results are shown for the affected pairs analyses (1. coffee never disturbs sleep; 2. coffee sometimes, usually or always disturbs sleep) and the threshold model analysis. Known genes related to caffeine effects in humans are shown, along with 2 candidate genes (DARPP-32, HCRT) under the 17q peak.