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.

中文翻译：

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捐赠者和接受者基因匹配分数和接受者基因型的联合测试对于寻找与移植结果相关的基因具有强大的力量。


移植供体和受体对之间的遗传匹配传统上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。我们评估了四个基因匹配评分，用于移植结果的关联分析。这些分数使用状态身份或两个基因组的遗传不相容性或不匹配来描述遗传祖先距离，因此可能反映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，与受体基因型联合测试这些分数是初步筛选和发现移植结果相关单核苷酸多态性 (SNP) 和基因区域的有力方法。在这些联合测试之后，分别对受体基因型和匹配评分进行边际测试，可以进一步了解移植结果背后的生物学机制。此外，我们还提出了肝移植数据分析结果，表明联合测试可以检测与肝移植急性排斥反应显着相关的 SNP。