MHC and KIR Sequencing and Association Analyses in the iGeneTRAiN Studies

iGeneTRAiN 研究中的 MHC 和 KIR 测序及关联分析

• 批准号: 10251946
• 负责人: KRZYSZTOF KIRYLUK
• 金额: $ 48.54万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-09-02 至 2025-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10251946
• 关键词: Acute; Address; Algorithms; Allografting; Amines; Amino Acid Motifs; Amino Acids; Antigens; Categories; Collaborations; Computerized Medical Record; DNA; Data; Data Set; Databases; Electrostatics; Epitopes; Failure; Generations; Genetic; Genetic Polymorphism; Genetic Research; Genomic approach; Genotype; Haplotypes; Heart; Heart Transplantation; Individual; Informed Consent; International; Kidney; Kidney Transplantation; Life; Ligands; Linkage Disequilibrium; Lung; Lung Transplantation; Measures; Methods; Natural Killer Cells; Nomenclature; Organ; Organ Transplantation; Outcome; Pathway interactions; Patients; Pear; Peptides; Phase; Phenotype; Pilot Projects; Play; Population; Procedures; Registries; Resolution; Retrospective Studies; Role; SNP genotyping; Salvelinus; Sampling; Savings; Serology; Solid; Structure; Surface; Training; Translational Research; Transplantation; Variant; Viral; analysis pipeline; base; clinically relevant; cohort; delayed graft function; end stage disease; exome sequencing; genetic architecture; genetic association; genetic variant; genome wide association study; genome-wide; genomic data; hematopoietic cell transplantation; human leukocyte antigen testing; human subject; improved; innovation; liver transplantation; novel; risk stratification; scaffold; scale up; three-dimensional modeling

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.

项目概要 HLA 供体-受体 (D-R) 匹配对于肾、心、肺移植术后的移植结果至关重要 和造血细胞移植。大型特征明确的遗传关联研究 缺乏移植队列，显然需要描述 MHC 和 KIR 的特征 遗传变异是移植结果的基础。国际遗传学与转化 移植网络研究 (iGeneTRAiN) 的成立是为了增进理解 通过整合移植研究来了解移植结果的遗传结构 包含来自超过 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 有史以来最大的实体器官移植联盟。战略制药合作 我们在大多数 iGeneTRAiN 研究中对关键的 HLA I 类和 II 类进行测序，并且 研究子集中的额外 MHC/KIR 区域正在促进充足的统计能力 评估 HLA 和 KIR 与关键移植相关结果的关联研究。一个大 iGeneTRAiN 数据库的一部分源自非欧洲血统样本，其中 极大地解决了这些人群中缺乏足够的 MHC/KIR 遗传数据的问题。