This twin study indicates a dose-response association between sleep problems and GERD, which remained after adjustment for genetic and familial environmental factors, as well as for sex, age, educational level, BMI and tobacco smoking.
When the results from the external analyses (including all twins) were compared with the results from the co-twin within-pair analyses for DZ and MZ twins (discordant for GERD), there were minor differences regarding “sometimes” having sleep problems, while the differences were slightly more pronounced for “often” having sleep problems. The association for “often” having sleep problems compared to “no” sleep problems was somewhat stronger among DZ twins compared to that of all twins, while the association was attenuated in the MZ twin analyses. Such a decrease in effect limited to MZ twins indicates genetic influence or limited statistical power, since the sample size for MZ twins was smaller than for the DZ twins. Measures of intrapair similarity (concordances and intraclass correlations) are greater for MZ than DZ pairs for GERD, supporting previous findings in this cohort that genetic factors are of moderate importance for GERD 
. However, the MZ:DZ differential is generally lower for indicators of sleep problems compared to two other twin studies 
, and in general suggests that familial environmental influences are more important than genetic factors for these measures of sleep problems. The lack of a difference in the cross-trait correlations for MZ and DZ pairs further supports the conclusion that there is no genetic or familial environmental confounding of the association between sleep problems and GERD.
In a previous population-based cross-sectional case-control study from our group, including 65,333 participants in the county of Nord-Trøndelag in Norway, a positive dose-response association between sleeplessness and GERD was found 
. Another population-based study using the 2006 US National Health and Wellness Survey of 41,319 participants found that participants with GERD had a two-fold increased occurrence of sleep difficulties compared to those without GERD 
. Thus, the results of these previous studies are well in line with the results of the present study, and this study further adds that the association persists after adjustment for heredity and family environment.
A proposed mechanism for sleep problems causing GERD is that sleep deprivation leads to esophageal hyperalgesia, i.e. patients with GERD are more pain sensitive to their reflux symptoms when sleep deprived 
. Another potential mechanism is that medications used for sleep disturbances might provoke or aggravate GERD 
. We observed no association between reflux medications and disturbed sleep. GERD, on the other hand, might cause or worsen sleep disturbances 
. Nocturnal reflux might lead to uneasy sleep and repeated awakenings, which are common in GERD patients 
. This was confirmed in the present study where an association between nocturnal reflux symptoms and disturbed sleep was observed. One model suggests a vicious circle, i.e., that sleep disturbances provoke reflux, which in turn worsens sleep problems, which in turn worsen GERD 
Strengths of the present study include the population-based design, the extensive data collection based on structured telephone interviews, and the ability to, for the first time, adjust for genetic and early environmental factors in addition to other known risk factors for GERD and sleep problems. Other advantages include the validated assessment of GERD 
consistent with the Montreal definition 
. Sleep problems were assessed using frequency of self-reported insomnia symptoms, which is commonly used in epidemiological studies 
. Limitations of the study include that only twins aged 65 years or older participated. The results might therefore not be generalizable to younger people. However, as the prevalence of both sleep problems and GERD is high in older ages 
, the results of this study should nevertheless be highly relevant. Another weakness is the cross-sectional study design, which prohibits evaluation of the direction of the association between sleep problems and GERD. However, this association is likely to be bidirectional 
In conclusion, this large population-based twin study indicates an association between sleep problems and GERD that remains after adjustment for heredity and familial environmental factors, as well as after other known risk factors for GERD and sleep problems.