Sun F, Ashley-Koch A E, Durham L K, Feingold E, Halloran M E, Manatunga A K, Sherman S L
Department of Genetics, Emory University School of Medicine, Atlanta, Georgia 30322, USA.
Genet Epidemiol. 1998;15(5):451-69. doi: 10.1002/(SICI)1098-2272(1998)15:5<451::AID-GEPI2>3.0.CO;2-3.
Several complex disorders are suspected of being associated with mitochondrial DNA (mtDNA) mutations. We studied the statistical properties of a test based on proband-relative pairs to identify potential mtDNA mutation involvement in a complex disorder. The test compares the recurrence risk of relatives of probands along the mitochondrial lineage with that of relatives along the nonmitochondrial lineage. If mtDNA mutations are involved, the recurrence risk will be higher among relatives in the mitochondrial lineage. The form of the test is independent of the assumed models of inheritance and interaction of the nuclear autosomal mutations with mtDNA mutations. The power of the test, however, differs among the different models and by the type of proband-relative pairs used in the test. We considered heterogeneity models with and without phenocopies, a three-state heteroplasmic mtDNA transmission model, and a multiplicative epistasis model. Under the heterogeneity model, the power of the test increases as the relationship between the proband and the relative becomes more distant. Under the multiplicative epistasis model, the power of the test decreases as the relationship between the proband and the relative becomes more distant.
几种复杂疾病被怀疑与线粒体DNA（mtDNA）突变有关。我们研究了一种基于先证者-亲属对的检验的统计特性，以确定潜在的mtDNA突变是否参与复杂疾病。该检验比较了沿线粒体谱系的先证者亲属与沿非线粒体谱系的亲属的复发风险。如果涉及mtDNA突变，线粒体谱系亲属中的复发风险将更高。检验的形式独立于核常染色体突变与mtDNA突变的假定遗传模型和相互作用模型。然而，检验的效能在不同模型之间以及检验中使用的先证者-亲属对的类型之间有所不同。我们考虑了有无拟表型的异质性模型、三状态异质性mtDNA传递模型和乘性上位性模型。在异质性模型下，检验的效能随着先证者与亲属之间的关系变得更远而增加。在乘性上位性模型下，检验的效能随着先证者与亲属之间的关系变得更远而降低。
