Abstract：
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.
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.
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.
Our findings suggest that subjective insomnia does not have a strong genetic signature mapping onto objective (polysomnographic) sleep variables.
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.
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.
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.
Our findings suggest that subjective insomnia does not have a strong genetic signature mapping onto objective (polysomnographic) sleep variables.
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.
摘要：
主观性失眠主诉和客观睡眠变化大多在临床试验研究之外进行研究。在这项研究中,在3项研究中,我们检测了与主观报道的失眠相关的240种遗传变异是否也与从多导睡眠图记录中提取的客观失眠参数相关.
研究样本（总计n=2,770）由威斯康星州睡眠队列（n=1,091）和男性骨质疏松性骨折（n=1,026）研究组成。两项基于人群的研究，和斯坦福睡眠队列,睡眠中心基于患者的样本(n=653)。与失眠定义的结果变量相关的七个客观多导睡眠图特征，每个变异等位基因作为预测因子。进行Meta回归，考虑常见的混杂因素以及研究之间的方差差异。此外,在评估客观失眠特征的独立线性混合模型中,为每个受试者生成归一化遗传风险评分作为预测变量.
多次测试校正后，与主观性失眠相关的单核苷酸多态性与7项客观睡眠指标中的6项无显著相关性.只有周期性肢体运动指数与rs113851554（MEIS1）显著相关，正如在以前的研究中发现的那样。标准化的遗传风险评分仅与唤醒指数和睡眠开始后的觉醒持续时间弱相关。
我们的研究结果表明，主观失眠没有强烈的遗传特征映射到客观（多导睡眠图）睡眠变量。
FoldagerJ,PeppardPE,HagenEW,etal.在2,770名成年人中，主观失眠报告的遗传风险仅与失眠的测谎仪弱相关。JClinSleepMed.2022年；18（1）：21-29。
研究样本（总计n=2,770）由威斯康星州睡眠队列（n=1,091）和男性骨质疏松性骨折（n=1,026）研究组成。两项基于人群的研究，和斯坦福睡眠队列,睡眠中心基于患者的样本(n=653)。与失眠定义的结果变量相关的七个客观多导睡眠图特征，每个变异等位基因作为预测因子。进行Meta回归，考虑常见的混杂因素以及研究之间的方差差异。此外,在评估客观失眠特征的独立线性混合模型中,为每个受试者生成归一化遗传风险评分作为预测变量.
多次测试校正后，与主观性失眠相关的单核苷酸多态性与7项客观睡眠指标中的6项无显著相关性.只有周期性肢体运动指数与rs113851554（MEIS1）显著相关，正如在以前的研究中发现的那样。标准化的遗传风险评分仅与唤醒指数和睡眠开始后的觉醒持续时间弱相关。
我们的研究结果表明，主观失眠没有强烈的遗传特征映射到客观（多导睡眠图）睡眠变量。
FoldagerJ,PeppardPE,HagenEW,etal.在2,770名成年人中，主观失眠报告的遗传风险仅与失眠的测谎仪弱相关。JClinSleepMed.2022年；18（1）：21-29。
