《科学杂志》:睡眠时体内氧浓度变化与遗传变异相关——雷氧科技快讯
2019-10-25

    摘要:据《科学杂志》2019 年10月24日发表的研究表明,睡眠期间的呼吸暂停会导致血液中氧含量水平变低,氧含量水平变低会增加心脏病、痴呆和死亡风险的疾病。研究人员已经发现了57种基因的遗传变异与睡眠期间血氧水平的下降密切相关。

    这项研究是由美国国家卫生研究院/国家心脏,肺和血液研究所资助所完成的。这项研究同时发表在《美国人类遗传学杂志》。 负责这项研究的科学家苏珊·雷德林(Susan Redline)表示:“一个人在睡眠期间的平均血氧水平是遗传性的,而且相对容易测量。“遗传基础的研究可以帮助解释为何有些人更容易睡眠呼吸紊乱并易于产生其相关疾病。”



    

     睡眠时有呼吸暂停会导致血液中的氧含量水平下降,如果有肺部出现问题或睡眠障碍往往进一步降低体内的氧含量水平,这是非常危险的情况。这些氧含量水平在睡眠期间的变化范围在个体之间差别很大,研究人员怀疑,这些可能很大程度上是受遗传因素的影响也会对基因变异产生影响。

     When we sleep, the oxygen level in our blood drops, due to interruptions in breathing. Lung and sleep disorders tend to decrease those levels further, and dangerously so. But the range of those levels during sleep varies widely between individuals and, researchers suspect, is greatly influenced by genetics.

   在健康结果中尽管血氧水平起着非常重要的作用,但遗传因素对其变异性的影响还是很缺乏。这些研究的发现会有助于更好的理解这一机制,特别是研究人员在对测试人群夜间睡眠氧气水平的测量,由于睡眠期间的呼吸紊乱给身体造成的相关的压力比白天水平更具变异性。

      Despite the key role blood oxygen levels play in health outcomes, the influence of genetics on their variability remains understudied. The current findings contribute to a better understanding, particularly because researchers looked at overnight measurements of oxygen levels. Those provide more variability than daytime levels due to the stresses associated with disordered breathing occurring during sleep.

    研究人员通过NHLBI精密医学(TOPMed)的跨组分程序的全基因组序列数据进行分析。为了加强数据分析的可靠性,他们也结合纳入了基于家族的连系分析的结果的方法,这是一种将遗传性特征带到基因组中位置的基因映射新方法。该方法也结合了来自于多个受特定紊乱影响的成员的家庭的数据。

   The researchers analyzed whole genome sequence data from the NHLBIs Trans-Omics for Precision Medicine TOPMed program. To strengthen the data, they incorporated results of family-based linkage analysis, a method for mapping genes that carry hereditary traits to their location in the genome. The method uses data from families with several members affected by a particular disorder.

     NHLBI肺病部主任詹姆斯·基利博士表示:“这项研究利用家庭数据寻找少数变异,这种方法在全基因组关联研究中经常被忽视。“它表明,当以家族联系数据为指导时,全基因组序列分析可以识别信号疾病风险的罕见变异,即使样本很小。在这种情况下,初始发现使用少于 500 个样本完成。

 “This study highlights the advantage of using family data in searching for rare variants, which is often missed in genome-wide association studies,“ said James Kiley, Ph.D., director of the Division of Lung Diseases at NHLBI. “It showed that, when guided by family linkage data, whole genome sequence analysis can identify rare variants that signal disease risks, even with a small sample. In this case, the initial discovery was done with fewer than 500 samples.

   新发现的57个DLC1基因变异与睡眠期间氧气水平的波动明显相关。事实上,他们解释了近1%的欧美人氧气含量的变异性,对于受无数变异影响的复杂遗传表型或特征来说,这种变异性相对较高。

      The newly identified 57 variants of the DLC1 gene were clearly associated with the fluctuation in oxygen levels during sleep. In fact, they explained almost 1% of the variability in the oxygen levels in European Americans, which is relatively high for complex genetic phenotypes, or traits, that are influenced by myriad variants.

    “ 值得注意的是,57种基因变异中,有51种“影响和调节人类肺成纤维细胞,一种在肺部产生疤痕组织的细胞,“研究作者、凯斯西储大学医学院教授朱晓峰博士说。他说,这很重要,因为"MENDELI随机分析,用于测试暴露与结果之间因果关系的统计方法,显示DLC1基因如何在爆炸和睡眠过程中改变氧水平的变化。"

        Notably, 51 of the 57 genetic variants “influence and regulate human lung fibroblast cells, a type of cell producing scar tissue in the lungs,“ said study author Xiaofeng Zhu, Ph.D., professor at the Case Western Reserve University School of Medicine. This is important, he said, because “Mendelian Randomization analysis, a statistical approach for testing causal relationship between an exposure and an outcome, shows a potential causal relationship between how the DLC1 gene modifies fibroblasts cells and the changes in oxygen levels during sleep.

        Kiley补充说,这种关系表明,一种共同的分子通路,或一种共同的机制,可能会影响一个人对睡眠紊乱呼吸和其他肺部疾病(如肺气肿)导致缺氧的易感性。

     This relationship, Kiley added, suggests that a shared molecular pathway, or a common mechanism, may be influencing a person‘s susceptibility to the lack of oxygen caused by sleep disordered breathing and other lung illnesses such as emphysema.


             资料援引:

         Story Source:

         Materials provided by NIH/National Heart, Lung and Blood Institute. Note: Content may be edited for style and length.

         Journal Reference:

         1.Jingjing Liang, Brian E. Cade, Karen Y. He, Heming Wang, Jiwon Lee, Tamar Sofer, Stephanie Williams, Ruitong Li, Han Chen, Daniel J. Gottlieb, Daniel S. Evans, Xiuqing Guo, Sina A. Gharib, Lauren Hale, David R. Hillman, Pamela L. Lutsey, Sutapa Mukherjee, Heather M. Ochs-Balcom, Lyle J. Palmer, Jessica Rhodes, Shaun Purcell, Sanjay R. Patel, Richa Saxena, Katie L. Stone, Weihong Tang, Gregory J. Tranah, Eric Boerwinkle, Xihong Lin, Yongmei Liu, Bruce M. Psaty, Ramachandran S. Vasan, Michael H. Cho, Ani Manichaikul, Edwin K. Silverman, R. Graham Barr, Stephen S. Rich, Jerome I. Rotter, James G. Wilson, Susan Redline, Xiaofeng Zhu. Sequencing Analysis at 8p23 Identifies Multiple Rare Variants in DLC1 Associated with Sleep-Related Oxyhemoglobin Saturation Level.American Journal of human genetics, 2019; doi: 10.1016/j.ajhg.2019.10.002

 

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