Department of Biostatistics, Epidemiology and Informatics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.
Division of Biostatistics, School of Public Health, University of Minnesota, Minneapolis, Minnesota.
Genet Epidemiol. 2020 Nov;44(8):893-907. doi: 10.1002/gepi.22349. Epub 2020 Aug 11.
Genetic matching between transplant donor and recipient pairs has traditionally focused on the human leukocyte antigen (HLA) regions of the genome, but recent studies suggest that matching for non-HLA regions may be important as well. We assess four genetic matching scores for use in association analyses of transplant outcomes. These scores describe genetic ancestry distance using identity-by-state, or genetic incompatibility or mismatch of the two genomes and therefore may reflect different underlying biological mechanisms for donor and recipient genes to influence transplant outcomes. Our simulation studies show that jointly testing these scores with the recipient genotype is a powerful method for preliminary screening and discovery of transplant outcome related single nucleotide polymorphisms (SNPs) and gene regions. Following these joint tests with marginal testing of the recipient genotype and matching score separately can lead to further understanding of the biological mechanisms behind transplant outcomes. In addition, we present results of a liver transplant data analysis that shows joint testing can detect SNPs significantly associated with acute rejection in liver transplant.
传统上，移植供体和受者对之间的遗传匹配主要集中在基因组的人类白细胞抗原（HLA）区域，但最近的研究表明，非 HLA 区域的匹配也可能很重要。我们评估了用于移植结果关联分析的四种遗传匹配评分。这些评分使用状态一致或两个基因组的遗传不兼容或不匹配来描述遗传亲缘关系距离，因此可能反映了供体和受体基因影响移植结果的不同潜在生物学机制。我们的模拟研究表明，联合测试这些评分与受者基因型是一种强大的方法，用于初步筛选和发现与移植结果相关的单核苷酸多态性（SNP）和基因区域。在对受者基因型和匹配评分分别进行边际测试后，联合测试可以进一步了解移植结果背后的生物学机制。此外，我们还介绍了肝移植数据分析的结果，表明联合测试可以检测到与肝移植中急性排斥反应显著相关的 SNP。
