Center for Sleep Medicine, Division of Pulmonary Medicine, Mayo Clinic, Scottsdale, AZ.
Chest. 2013 May;143(5):1489-1499. doi: 10.1378/chest.12-1219.
The study of genetics is providing new and exciting insights into the pathogenesis, diagnosis, and treatment of disease. Both normal sleep and several types of sleep disturbances have been found to have significant genetic influences, as have traits of normal sleep, such as those evident in EEG patterns and the circadian sleep-wake cycle. The circadian sleep-wake cycle is based on a complex feedback loop of genetic transcription over a 24-h cycle. Restless legs syndrome (RLS) and periodic limb movements in sleep (PLMS) have familial aggregation, and several genes have a strong association with them. Recent genome-wide association studies have identified single nucleotide polymorphisms linked to RLS/PLMS, although none has a definite functional correlation. Narcolepsy/cataplexy are associated with HLA DQB1*0602 and a T-cell receptor α locus, although functional correlations have not been evident. Obstructive sleep apnea is a complex disorder involving multiple traits, such as anatomy of the oropharynx, ventilatory control, and traits associated with obesity. Although there is clear evidence of familial aggregation in the obstructive sleep apnea syndrome, no specific gene or locus has been identified for it. Angiotensin-converting enzyme has been proposed as a risk variant, but evidence is weak. Fatal familial insomnia and advanced sleep phase syndrome are sleep disorders with a definite genetic basis.
遗传学研究为疾病的发病机制、诊断和治疗提供了新的、令人兴奋的见解。正常睡眠和几种类型的睡眠障碍都被发现有显著的遗传影响，正常睡眠的特征也是如此，如脑电图模式和昼夜节律睡眠-觉醒周期中所表现出来的特征。昼夜节律睡眠-觉醒周期是基于一个复杂的基因转录反馈循环，在 24 小时周期内进行。不宁腿综合征（RLS）和睡眠周期性肢体运动（PLMS）具有家族聚集性，并且有几个基因与它们有很强的关联。最近的全基因组关联研究已经确定了与 RLS/PLMS 相关的单核苷酸多态性，尽管没有一个具有明确的功能相关性。发作性睡病/猝倒与 HLA DQB1*0602 和 T 细胞受体 α 基因座有关，尽管没有明显的功能相关性。阻塞性睡眠呼吸暂停是一种涉及多种特征的复杂疾病，如口咽解剖结构、通气控制和与肥胖相关的特征。尽管阻塞性睡眠呼吸暂停综合征有明显的家族聚集证据，但尚未确定其特定的基因或基因座。血管紧张素转换酶被认为是一种风险变异体，但证据较弱。致命性家族性失眠症和睡眠相位延迟综合征是具有明确遗传基础的睡眠障碍。
