Jonathan Foldager1,2,3, Paul E Peppard4, Erika W Hagen4, Katie L Stone5, Daniel S Evans5, Gregory J Tranah5, Helge Sørensen2, Poul Jennum6, Emmanuel Mignot3, Logan D Schneider3,7,8. 1. Department of Applied Mathematics and Computer Science, Technical University of Denmark, Kgs. Lyngby, Denmark. 2. Department of Health Technology, Technical University of Denmark, Kgs. Lyngby, Denmark. 3. Stanford Center for Sleep Sciences and Medicine, Stanford University, Palo Alto, California. 4. Department of Population Health Sciences, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, Wisconsin. 5. Research Institute, California Pacific Medical Center, San Francisco, California. 6. Danish Center for Sleep Medicine, Department of Clinical Neurophysiology, Rigshospitalet, Glostrup, Denmark. 7. Stanford/VA Alzheimer's Research Center, Palo Alto, California. 8. Sierra Pacific Mental Illness Research Education and Clinical Centers, VA Palo Alto Health Care System, Palo Alto, California.
Abstract
STUDY OBJECTIVES: Subjective insomnia complaints and objective sleep changes are mostly studied outside of clinical trial studies. In this study, we tested whether 240 genetic variants associated with subjectively reported insomnia were also associated with objective insomnia parameters extracted from polysomnographic recordings in three studies. METHODS: The study sample (total n = 2,770) was composed of the Wisconsin Sleep Cohort (n = 1,091) and the Osteoporotic Fractures in Men (n = 1,026) study, two population-based studies, and the Stanford Sleep Cohort, a sleep center patient-based sample (n = 653). Seven objective polysomnographic features related to insomnia defined outcome variables, with each variant allele serving as predictor. Meta-regression was performed, accounting for common confounders as well as variance differences between studies. Additionally, a normalized genetic risk score was generated for each subject to serve as a predictor variable in separate linear mixed models assessing objective insomnia features. RESULTS: After correction for multiple testing, single-nucleotide polymorphisms associated with subjective insomnia were not significantly associated with 6 of 7 objective sleep measures. Only periodic limb movement index was significantly associated with rs113851554 (MEIS1), as found in previous studies. The normalized genetic risk score was only weakly associated with arousal index and duration of wake after sleep onset. CONCLUSIONS: Our findings suggest that subjective insomnia does not have a strong genetic signature mapping onto objective (polysomnographic) sleep variables. CITATION: Foldager J, Peppard PE, Hagen EW, et al. Genetic risk for subjective reports of insomnia associates only weakly with polygraphic measures of insomnia in 2,770 adults. J Clin Sleep Med. 2022;18(1):21-29.
STUDY OBJECTIVES: Subjective insomnia complaints and objective sleep changes are mostly studied outside of clinical trial studies. In this study, we tested whether 240 genetic variants associated with subjectively reported insomnia were also associated with objective insomnia parameters extracted from polysomnographic recordings in three studies. METHODS: The study sample (total n = 2,770) was composed of the Wisconsin Sleep Cohort (n = 1,091) and the Osteoporotic Fractures in Men (n = 1,026) study, two population-based studies, and the Stanford Sleep Cohort, a sleep center patient-based sample (n = 653). Seven objective polysomnographic features related to insomnia defined outcome variables, with each variant allele serving as predictor. Meta-regression was performed, accounting for common confounders as well as variance differences between studies. Additionally, a normalized genetic risk score was generated for each subject to serve as a predictor variable in separate linear mixed models assessing objective insomnia features. RESULTS: After correction for multiple testing, single-nucleotide polymorphisms associated with subjective insomnia were not significantly associated with 6 of 7 objective sleep measures. Only periodic limb movement index was significantly associated with rs113851554 (MEIS1), as found in previous studies. The normalized genetic risk score was only weakly associated with arousal index and duration of wake after sleep onset. CONCLUSIONS: Our findings suggest that subjective insomnia does not have a strong genetic signature mapping onto objective (polysomnographic) sleep variables. CITATION: Foldager J, Peppard PE, Hagen EW, et al. Genetic risk for subjective reports of insomnia associates only weakly with polygraphic measures of insomnia in 2,770 adults. J Clin Sleep Med. 2022;18(1):21-29.
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