STATISTICAL STUDIES OF MTDNA INVOLVEMENT IN DISEASES

描述：(改编自《调查人员摘要》)本报告的目的 研究是开发统计方法来评估线粒体 DNA(MtDNA)突变与疾病的病因学有关 估计线粒体DNA突变对疾病的贡献。具体的 目标如下：(1)提出抽样方案和检验统计 确定线粒体DNA突变是否与一种疾病有关；比较其威力 使用假设线粒体DNA的不同抽样方案的测试统计数据 突变与疾病有关；(2)研究线粒体DNA突变是否与疾病有关 疾病的主要原因或核突变也可能与此有关。 在疾病的病因学中；在后一种情况下，研究相互作用 线粒体DNA突变和核突变之间的关系；以及(3)估计 线粒体DNA突变对疾病的贡献。 将对本研究中开发的测试方法进行评估和验证 通过模拟研究，并将应用于一系列系谱 对于Leber遗传性视神经病变(LHON)，一种已知的疾病 与线粒体DNA突变有关。 测试方法和统计方法将应用于现场研究 胰岛素依赖性糖尿病(IDDM)。在以下方面继续合作 在这个项目的期限内，还将研究其他复杂的疾病。

DESCRIPTION: (Adapted from Investigator's Abstract) The objective of this research is to develop statistical methods to assess whether mitochondrial DNA (mtDNA) mutations are involved in the etiology of disease and to estimate the contribution of mtDNA mutations to the disease. The specific aims are as follow: (1) to propose sampling schemes and test statistics to identify if mtDNA mutations are involved in a disease; to compare the power of the test statistics using different sampling schemes assuming mtDNA mutations are involved in the disease; (2) to study if mtDNA mutations are the primary cause of the disease or nuclear mutations may also be involved in the etiology of the disease; in the later case, study the interaction between mtDNA mutations and nuclear mutations; and (3) to estimate the contribution of mtDNA mutations to the disease. The test methods developed in this study will be evaluated and validated through simulation studies and will be applied to a collection of pedigrees for Leber's hereditary optic neuropathy (LHON), a disease known to be related to mtDNA mutations. The test methods and statistics will be applied to field studies on insulin-dependent diabetes mellitus (IDDM). Continuing collaborations on other complex diseases will be sought during the tenure of this project.