Family-based mitochondrial association study of traits related to type 2 diabetes and the metabolic syndrome in adolescents
Family-based mitochondrial association study of traits related to type 2 diabetes and the metabolic syndrome in adolescents
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DOI：
10.1007/s00125-009-1510-9
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发表时间：
2009-11-01
期刊：
影响因子：
8.2
通讯作者：
Montgomery, G. W.
中科院分区：
文献类型：
--
作者：
Byrne, E. M.;McRae, A. F.;Montgomery, G. W.
目的/假设线粒体在2型糖尿病和代谢综合征的病因学中的潜在作用一直备受关注，并且已经针对这些病症进行了许多病例对照线粒体关联研究。我们测试了一个潜在的关联之间的共同线粒体变异和一些数量的数量性状相关的2型糖尿病在一个大样本>2,000健康的澳大利亚青少年双胞胎和他们的兄弟姐妹，其中许多人进行了测量，在不止一次的once.Methods据我们所知，这是第一个线粒体关联研究的数量性状进行家庭数据。线粒体的母系遗传模式意味着已建立的关联方法不适用于家庭线粒体数据的分析。我们提出了一种方法，在免费提供的程序Sib-对执行这样的analysis.Results尽管我们的研究有能力检测这些表型的影响不大的变体，只有一个显着的关联后，发现校正在任何四个年龄组的多个测试。这是针对具有三酰甘油水平的mt 14365（未校正的p=0.0006）。这种关联没有复制在其他年龄组。结论/解释我们发现很少有证据表明，在我们的样本中，常见的欧洲线粒体变异有助于糖尿病相关的定量表型的变化。在我们的样本中，只有一个变体显示出显著的关联，这种关联需要在更大的队列中复制。此类重复研究或未来的荟萃分析可能会揭示更多由于样本量限制而无法检测到的微妙效应。
Aims/hypothesis There has been much focus on the potential role of mitochondria in the aetiology of type 2 diabetes and the metabolic syndrome, and many case control mitochondrial association studies have been undertaken for these conditions. We tested for a potential association between common mitochondrial variants and a number of quantitative traits related to type 2 diabetes in a large sample of >2,000 healthy Australian adolescent twins and their siblings, many of whom were measured on more than one occasion.Methods To the best of our knowledge, this is the first mitochondrial association study of quantitative traits undertaken using family data. The maternal inheritance pattern of mitochondria means established association methodologies are unsuitable for analysis of mitochondrial data in families. We present a methodology, implemented in the freely available program Sib-Pair for performing such an analysis.Results Despite our study having the power to detect variants with modest effects on these phenotypes, only one significant association was found after correction for multiple testing in any of four age groups. This was for mt14365 with triacylglycerol levels (unadjusted p=0.0006). This association was not replicated in other age groups.Conclusions/interpretation We find little evidence in our sample to suggest that common European mitochondrial variants contribute to variation in quantitative phenotypes related to diabetes. Only one variant showed a significant association in our sample, and this association will need to be replicated in a larger cohort. Such replication studies or future meta-analyses may reveal more subtle effects that could not be detected here because of limitations of sample size.