STATISTICAL STUDIES OF MTDNA INVOLVEMENT IN DISEASES

描述：（改编自研究者摘要）本研究的目的 研究是开发统计方法来评估线粒体是否 DNA（mtDNA）突变与疾病的病因有关， 估计mtDNA突变对疾病的贡献。 具体 目的如下：（1）提出抽样方案和检验统计量， 确定mtDNA突变是否与疾病有关;比较 使用不同的抽样方案，假设mtDNA的检验统计 突变参与疾病;（2）研究mtDNA突变是否与疾病有关。 疾病的主要原因或核突变也可能涉及 在疾病的病因学;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;（3）估计 mtDNA突变对疾病的影响 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，并将其应用于一系列谱系， Leber遗传性视神经病变（LHON），一种已知 与mtDNA突变有关。 测试方法和统计数据将应用于实地研究， 胰岛素依赖型糖尿病（IDDM）。 继续合作 在本项目实施期间，将寻求其他复杂疾病。

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.