van der Spek Ashley, Luik Annemarie I, Kocevska Desana, Liu Chunyu, Brouwer Rutger W W, van Rooij Jeroen G J, van den Hout Mirjam C G N, Kraaij Robert, Hofman Albert, Uitterlinden André G, van IJcken Wilfred F J, Gottlieb Daniel J, Tiemeier Henning, van Duijn Cornelia M, Amin Najaf
Department of Epidemiology, Erasmus Medical Center, Rotterdam, Netherlands.
Sleep and Circadian Neuroscience Institute, Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, United Kingdom.
Front Genet. 2017 Oct 18;8:151. doi: 10.3389/fgene.2017.00151. eCollection 2017.
Obstructive sleep apnea (OSA) is a common sleep breathing disorder associated with an increased risk of cardiovascular and cerebrovascular diseases and mortality. Although OSA is fairly heritable (~40%), there have been only few studies looking into the genetics of OSA. In the present study, we aimed to identify genetic variants associated with symptoms of sleep apnea by performing a whole-exome sequence meta-analysis of symptoms of sleep apnea in 1,475 individuals of European descent. We identified 17 rare genetic variants with at least suggestive evidence of significance. Replication in an independent dataset confirmed the association of a rare genetic variant (rs2229918; minor allele frequency = 0.3%) with symptoms of sleep apnea (-value = 6.98 × 10, β = 0.99). Rs2229918 overlaps with the 3' untranslated regions of and genes on chromosome 19q13. Both genes are expressed in tissues in the neck area, such as the tongue, muscles, cartilage and the trachea. Further, is localized in the nucleus and mitochondria and involved in the tumor necrosis factor-alpha/nuclear factor kappa B signaling pathway. Our results and biological functions of / genes suggest that the 19q13 locus is interesting for further OSA research.
阻塞性睡眠呼吸暂停（OSA）是一种常见的睡眠呼吸障碍，与心血管和脑血管疾病风险增加及死亡率升高相关。尽管OSA具有较高的遗传性（约40%），但对其遗传学的研究却很少。在本研究中，我们旨在通过对1475名欧洲血统个体的睡眠呼吸暂停症状进行全外显子序列荟萃分析，来识别与睡眠呼吸暂停症状相关的基因变异。我们鉴定出17个罕见的基因变异，至少有提示性的显著证据。在一个独立数据集中进行的重复验证证实了一个罕见基因变异（rs2229918；次要等位基因频率 = 0.3%）与睡眠呼吸暂停症状相关（P值 = 6.98 × 10⁻⁶，β = 0.99）。Rs2229918与19号染色体q13上的 和 基因的3'非翻译区重叠。这两个基因均在颈部区域的组织中表达，如舌头、肌肉、软骨和气管。此外， 定位于细胞核和线粒体，并参与肿瘤坏死因子-α/核因子κB信号通路。我们的结果以及 / 基因的生物学功能表明，19q13位点对于进一步开展OSA研究具有重要意义。
