Genome-wide association study of serum coenzyme Q10 levels identifies susceptibility loci linked to neuronal diseases
Genome-wide association study of serum coenzyme Q10 levels identifies susceptibility loci linked to neuronal diseases
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DOI：
10.1093/hmg/ddw134
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发表时间：
2016-07-01
影响因子：
3.5
通讯作者：
Onur, Simone
中科院分区：
文献类型：
--
作者：
Degenhardt, Frauke;Niklowitz, Petra;Onur, Simone
辅酶Q（10）（CoQ（10））是一种亲脂性氧化还原分子，存在于人体组织中几乎所有细胞的膜中。辅酶Q（10）是呼吸运输链所必需的，是炎症过程和基因表达的调节剂。罕见的单基因辅酶Q（10）缺乏症在具有高能量需求的组织（例如肾脏）和细胞类型（例如神经元）中显示出明显的症状。为了确定影响血清辅酶Q（10）水平的常见遗传变异，我们在两个独立的横断面北方德国队列中进行了固定效应荟萃分析，共包括1300人。我们确定了两个全基因组的显着易感基因座。最相关的单核苷酸多态性（SNP）是18号染色体上COLEC 12基因内的rs 9952641（P值= 1.31 x 10（-8），β = 0.063，CI 0.95 [0.041，0.085]）。2号染色体上NRXN-1基因rs 933585位点的SNP也显示出全基因组的显著性（P值= 3.64 × 10（-8），β =-0.034，CI0.95 [-0.046，-0.022]）。这两种基因以前都与阿尔茨海默病、自闭症和精神分裂症等神经元疾病有关。在我们的“前10名”相关变异中，另外四个已知神经元连接的基因座显示出与辅酶Q（10）水平的暗示性关联。总之，这项研究表明，血清辅酶Q（10）水平与神经元疾病相关的常见遗传位点有关。
Coenzyme Q(10) (CoQ(10)) is a lipophilic redox molecule that is present in membranes of almost all cells in human tissues. CoQ(10) is, amongst other functions, essential for the respiratory transport chain and is a modulator of inflammatory processes and gene expression. Rare monogenetic CoQ(10) deficiencies show noticeable symptoms in tissues (e.g. kidney) and cell types (e.g. neurons) with a high energy demand. To identify common genetic variants influencing serum CoQ(10) levels, we performed a fixed effects meta-analysis in two independent cross-sectional Northern German cohorts comprising 1300 individuals in total. We identified two genome-wide significant susceptibility loci. The best associated single nucleotide polymorphism(SNP) was rs9952641 (P value = 1.31 x 10(-8), beta = 0.063, CI0.95 [0.041, 0.085]) within the COLEC12 gene on chromosome 18. The SNP rs933585 within the NRXN-1 gene on chromosome 2 also showed genome wide significance (P value = 3.64 x 10(-8), beta = -0.034, CI0.95 [-0.046, -0.022]). Both genes have been previously linked to neuronal diseases like Alzheimer's disease, autism and schizophrenia. Among our 'top-10' associated variants, four additional loci with known neuronal connections showed suggestive associations with CoQ(10) levels. In summary, this study demonstrates that serum CoQ(10) levels are associated with common genetic loci that are linked to neuronal diseases.