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

基本信息

批准号：
10020606
负责人：
KRZYSZTOF KIRYLUK
金额：
$ 51.19万
依托单位：
UNIVERSITY OF PENNSYLVANIA
依托单位国家：
美国
项目类别：
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/10020606
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 Risk stratification Role SNP genotyping Salvelinus Sampling Savings Serological 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 scaffold scale up three-dimensional modeling

项目摘要

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) 的成立是为了增进了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，并且研究子集中额外的 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。