MHC and KIR Sequencing and Association Analyses in the iGeneTRAiN Studies

项目总结 人类白细胞抗原供受者(D-R)配型对肾、心、肺等器官移植预后至关重要 和造血细胞移植。大型遗传关联研究具有良好的特征 移植队列缺乏，显然需要确定MHC和KIR是如何 基因变异是移植结果的基础。国际遗传学与翻译学 移植研究网络(IGeneTRAiN)的成立是为了增加人们对移植的了解 通过将移植研究汇集在一起，研究移植结果的遗传结构 使用来自&gt；52,600名接受者/捐赠者的全基因组关联研究(GWAS)数据集 精心策划的心脏、肾脏、肝脏和肺移植表型数据集。这构成了 有史以来最大的固体器官移植联盟。战略性的医药合作 在大多数iGeneTRAiN研究中，我们对关键的人类白细胞抗原I类和II类进行了排序，以及 研究子集中的其他MHC/KIR区域正在促进充足的统计能力 评估人类白细胞抗原和KIR与移植相关关键结果的相关性研究。大号 IGeneTRAiN数据库的一部分来自非欧洲血统样本，这 极大地解决了这些人群缺乏足够的MHC/KIR基因数据的问题。

PROJECT SUMMARY HLA donor-recipient (D-R) matching is critical for graft outcomes following Kidney, Heart, Lung and hematopoietic cell transplantation. Genetic association studies in large well-characterized transplant cohorts are lacking and there is a clear need to characterize how MHC and KIR genetic variants underpin transplantation outcomes. The International Genetics & Translational Research in Transplantation Network (iGeneTRAiN) was formed to increase the understanding of the genetic architecture of transplant outcomes, by bringing together transplantation studies with genome-wide association study (GWAS) datasets from >52,600 recipients/donors across well-curated heart, kidney, liver and lung transplant phenotype datasets. This constitutes the largest solid-organ transplant consortium ever assembled. A strategic Pharma collaboration where we sequence key HLA Class I and II in the majority of iGeneTRAiN studies, and additional MHC/KIR regions in subsets of studies, is facilitating ample statistical power to assess association studies of HLA and KIR with key transplant-related outcomes. A large portion of the iGeneTRAiN database is derived from non-European ancestry samples, which greatly addresses the lack of adequate MHC/KIR genetic data in these populations.