STUDIES OF OBSTRUCTIVE SLEEP APNEA

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 来自连锁分析和基于关联的分析的证据表明载脂蛋白E（ApoE）是阻塞性睡眠呼吸暂停的疾病易感位点。为了进一步评估ApoE在睡眠呼吸暂停中的假定作用，我们对一个队列进行了基因分型、关联和连锁分析，以调查睡眠呼吸暂停的遗传流行病学。在一个高加索家庭的子集，10个微卫星，跨越20 cM，基因型在19号染色体上的ApoE附近的区域，以前的暗示连锁已被证明使用9.1 cM全基因组扫描。用这些精细定位标记（n=196个同胞对，56个家庭）进行的Haseman-Elston回归分析显示与标记AFM 210 yg 9（p=0.00034）连锁的证据，其比用原始扫描观察到的增加。还对来自具有可用DNA的队列的较大数据集（n= 1，211，来自271个家庭，年龄3-85岁）进行ApoE基因分型。为了确定ApoE基因型是否解释了连锁峰，我们将ApoE基因型作为协变量纳入回归模型。纳入ApoE E2等位基因作为协变量使回归系数降低18%，表明ApoE不能实质性解释连锁信号。最后，我们在1，211名个体的较大样本中重复了基于关联的分析，并观察到具有ApoE E2等位基因的个体中睡眠呼吸暂停的患病率较高。总的来说，证据表明，在ApoE区域存在阻塞性睡眠呼吸暂停的疾病易感位点，但ApoE本身不太可能是致病位点。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Evidence from both linkage analyses and association-based analyses has implicated Apoliprotein E (ApoE) as a disease susceptibility locus for obstructive sleep apnea. To further assess the putative role of ApoE in sleep apnea, we performed genotyping, association, and linkage analyses in a cohort assembled to investigate the genetic epidemiology of sleep apnea. Among a subset of the Caucasian families, ten microsatellites, spanning 20 cM, were genotyped in a region near ApoE on chromosome 19 where previous suggestive linkage had been demonstrated using a 9.1-cM genome-wide scan. Haseman-Elston regression analysis, conducted with these fine mapping markers (n=196 sibling pairs, 56 families), showed evidence for linkage to marker AFM210yg9 (p=0.00034), which was increased over that observed with the original scan. ApoE genotyping also was performed on a larger set of data (n=1,211 from 271 families, ages 3-85 years) from the cohort with available DNA. To determine whether the ApoE genotype explains the linkage peak, we included the ApoE genotype as a covariate in regression models. Inclusion of ApoE E2 allele as a covariate reduced the regression coefficient by 18%, suggesting that ApoE does not substantively explain the linkage signal. Finally, we repeated an association-based analysis in the larger sample of 1,211 individuals, and observed a higher prevalence of sleep apnea among individuals with the ApoE E2 allele. Overall, the evidence suggests that there is a disease susceptibility locus for obstructive sleep apnea in the region of ApoE, but ApoE itself is unlikely to be the causative locus.