Patel S R, Larkin E K, Redline S
Division of Pulmonary, Critical Care and Sleep Medicine, Department of Medicine, University Hospitals Case Medical Center, and Case Western Reserve University, Cleveland, OH 44106, USA.
Int J Obes (Lond). 2008 May;32(5):795-800. doi: 10.1038/sj.ijo.0803803. Epub 2008 Jan 22.
Obesity and obstructive sleep apnea each have a substantial genetic basis and commonly coexist in individuals. The degree to which the genetic underpinnings for these disorders overlap has not been previously quantified.
A total of 1802 individuals from 310 families in the Cleveland Family Study underwent home sleep studies as well as standardized assessment of body mass index (BMI) and circumferences at the waist, hip and neck. In 713 participants with laboratory sleep studies, fasting blood samples were assayed for leptin, adiponectin and resistin. Variance component models were used to estimate heritability and genetic correlations.
The heritability of the apnea hypopnea index (AHI) was 0.37+/-0.04 and 0.33+/-0.07 for home and laboratory sleep studies, respectively. The genetic correlations between AHI and anthropomorphic adiposity measures ranged from 0.57 to 0.61, suggesting that obesity can explain nearly 40% of the genetic variance in sleep apnea. The magnitude of the genetic correlations between apnea severity and adipokine levels was substantially less than those with anthropomorphic measures, ranging from 0.11 to 0.46. After adjusting for BMI, no significant genetic correlation with apnea severity was observed for any of the other adiposity measures.
Substantial but not complete overlap in genetic bases exists between sleep apnea and anthropomorphic indices of adiposity, and this overlap accounts for more than one-third of the genetic variance in apnea severity. These findings suggest that genetic polymorphisms exist that importantly influence sleep apnea susceptibility through both obesity-dependent and -independent pathways.
肥胖和阻塞性睡眠呼吸暂停均有坚实的遗传基础，且在个体中常同时存在。此前尚未对这些疾病的遗传基础重叠程度进行量化。
克利夫兰家族研究中来自310个家庭的1802名个体接受了家庭睡眠研究以及体重指数（BMI）和腰围、臀围及颈围的标准化评估。在713名进行了实验室睡眠研究的参与者中，采集空腹血样检测瘦素、脂联素和抵抗素。采用方差成分模型估计遗传力和遗传相关性。
对于家庭睡眠研究和实验室睡眠研究，呼吸暂停低通气指数（AHI）的遗传力分别为0.37±0.04和0.33±0.07。AHI与人体测量肥胖指标之间的遗传相关性在0.57至0.61之间，这表明肥胖可解释睡眠呼吸暂停近40%的遗传变异。呼吸暂停严重程度与脂肪因子水平之间的遗传相关性强度明显低于与人体测量指标的相关性，范围在0.11至0.46之间。在调整BMI后，未观察到其他任何肥胖指标与呼吸暂停严重程度之间存在显著遗传相关性。
睡眠呼吸暂停与人体测量肥胖指标之间存在显著但不完全的遗传重叠，且这种重叠占呼吸暂停严重程度遗传变异的三分之一以上。这些发现表明存在重要影响睡眠呼吸暂停易感性的基因多态性，其通过肥胖依赖和非依赖途径发挥作用。
