小柯机器人

英国剑桥大学Joanna M. M. Howson及Patrick F. Chinnery课题组合作的研究揭示了英国生物样本库中线粒体DNA（mtDNA）基因型和表型的关联图集。该项研究成果发表在2021年5月17日出版的《自然-遗传学》上。

利用研发的用于大规模分析mtDNA变异的工作流程，研究人员揭示了英国人群中细胞核和线粒体基因组结构之间的相关性，并建立了英国生物库mtDNA表型关联的参考图集。共有260个mtDNA-表型新关联被发现（P <1×10^-5），包括与2型糖尿病有关的rs2853822/m.8655 C>T（MT-ATP6）、与多发性硬化症有关的rs878966690/m.13117 A>G（MT- ND5）、与成人身高相关的6 种mtDNA关联、与2种肝脏生物标志物有关的24种 mtDNA关联以及与肾功能参数有关的16种 mtDNA关联。

基于稀有变异基因的测试发现线粒体复合物I基因调节平均红细胞体积和平均红细胞血红蛋白。七个性状既具有罕见的mtDNA关联又具有常见的mtDNA关联，其中罕见的变异往往比常见的变异能产生更大的影响。该工作阐明了在常见复杂疾病中研究mtDNA变异的价值，并为未来大规模mtDNA关联研究奠定了基础。

研究人员表示，常见疾病个体的线粒体DNA变异尚未得到充分研究，部分原因是缺乏基因型检测和质量控制的方法。

附：英文原文

Title: An atlas of mitochondrial DNA genotype–phenotype associations in the UK Biobank

Author: Ekaterina Yonova-Doing, Claudia Calabrese, Aurora Gomez-Duran, Katherine Schon, Wei Wei, Savita Karthikeyan, Patrick F. Chinnery, Joanna M. M. Howson

Issue&Volume: 2021-05-17

Abstract: Mitochondrial DNA (mtDNA) variation in common diseases has been underexplored, partly due to a lack of genotype calling and quality-control procedures. Developing an at-scale workflow for mtDNA variant analyses, we show correlations between nuclear and mitochondrial genomic structures within subpopulations of Great Britain and establish a UK Biobank reference atlas of mtDNA–phenotype associations. A total of 260 mtDNA–phenotype associations were new (P<1×105), including rs2853822/m.8655C>T (MT-ATP6) with type 2 diabetes, rs878966690/m.13117A>G (MT-ND5) with multiple sclerosis, 6 mtDNA associations with adult height, 24 mtDNA associations with 2 liver biomarkers and 16 mtDNA associations with parameters of renal function. Rare-variant gene-based tests implicated complex I genes modulating mean corpuscular volume and mean corpuscular hemoglobin. Seven traits had both rare and common mtDNA associations, where rare variants tended to have larger effects than common variants. Our work illustrates the value of studying mtDNA variants in common complex diseases and lays foundations for future large-scale mtDNA association studies.

DOI: 10.1038/s41588-021-00868-1

Source: https://www.nature.com/articles/s41588-021-00868-1

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