Overview for Researchers

The overarching goal of iGeneTRAiN is to assemble and deeply integrate highly characterized solid-organ transplant phenotypes with genomic and other omic datasets, and transitions to translational research for early detection of pre and post-transplant complications. iGeneTRAIN is currently progressing through three phases shown below

Phase 1: Phase 1 has largely been organizational, focusing on maximizing the existing data for genome-wide association studies (GWAS) of transplant related phenotypes, from consortium members. Under Phase 1, we have, and continue to, assemble phenotypic and genetic data from existing solid organ transplant (SOT) and hematopoietic stem cell transplant (HSCT) studies. For clinical phenotyping datasets, we have been collating and harmonizing phenotype measures that that are being used in additional analyses (Phase 2). For genetic datasets, we have collated information from different genetic datasets, creating a comprehensive catalog of biomarkers derived from 1) genome-wide genotyping and 2) second generation sequencing (SGS) for genome-wide association studies (GWAS) and 3) copy number variant (CNV) and candidate gene studies for primary/end-stage disease studies. Ultimately, this is facilitating data meta-analyses and replication studies across the consortium.

Phase 1a (completed for the majority of existing studies): Surveying and collating the relevant covariate, phenotypic and outcome data information among existing and pending studies across various sites and organ procurement organizations. Phase I studies can also include DNA-only studies which are being leveraged in replication studies and in new SGS and GWG studies, some of which are funded through NIH and Industry sponsorship. 

Phase 1b: Formed phenotype-specific working groups. These primarily include four groups focused on solid organ transplant (heart, kidney and liver) with small numbers of hematopoietic stem cell transplant datasets aggregated to date. Respective groups focused on collating, harmonization and formatting of relevant phenotypes and covariates for analyses.

Phase 1c: Formation of four additional working groups whose interests intersect across different transplant phenotypes. These groups are:

  • HLA working group
  • Genomic and multiomics groups 
  • Pharmacogenomics
  • Steering committee (comprised of representative’s various workgroups).

Phase 2 has been building upon existing single-site and initial meta-analyses and conducting broader meta-analyses studies across additional iGeneTRAIN single-organ and cross-organ studies. These have been completed for a number of solid-organ specific, and cross-organ specific analyses. We have embarked on additional RNA expression, proteomic, and functional studies using biological materials collected from the respective studies. These have been performed to data on a number of NIH funded studies including A-WISH, A2ALL, BioTIP, CTOT-03 and a number of national and international heart transplant studies). 

Phase 3, entails deeper harmonization of the consortium’s activities (once the majority of the single site publications have been completed) and establishing long-term sustainability through large national and international grants (a number of which have recently been awarded through NIAID/NIH), and with Industry collaborations.

Existing genomics studies, HLA and New Onset of Diabetes after Transplant and Acute Rejection outcomes
Organ Study Genotyping/SGS Platform Number of Variants Directly Captured Current existing Imputation Data HLA Outcomes
2-Digit Resolution 4-Digit Resolution NODAT (%) AR (%)
Kidney Go-CAR HumanOmniExpress ~900K Imputed by IMPUTE2 and MACH at two independent sites using 1KGPv3 reference set Yes Yes NA 10
TRANSPLANT-LINES Axiom Tx SNP GWAS array ~780K Imputed by Impute2 at UMCU and Penn state using 1KGv3 and GoNLv5 Yes No 21 34
Vanderbilt BioVU Infinium 660K, Omni1M ~660K to 1 Million Imputed by IMPUTE2 at Vanderbilt using 1KGPv3 Yes Yes, since 2006 15 17
CHOP-Kidney Tx Axiom Tx SNP GWAS array ~780K Imputed by Impute2 at UMCU and Penn state using 1KGv3 and GoNLv5 Yes Yes 2 0.3
UPenn-Kidney Tx Axiom Tx SNP GWAS array ~780K Imputed by IMPUTE2 at Penn State using 1KGPv3 Yes No 10 25
WTCCC-3 Infinium 660K ~660K Imputed by IMPUTE2 at Sanger Institute using 1KGPv3 Yes (subset) Yes (subset) N/A 19
GEN-03 DeKAF Genomics Axiom Tx SNP GWAS array ~780K Imputed by Impute2 at UMCU and Penn state using 1KGv3 and GoNLv5 Yes (from clinic & from GWAS) Yes (imputed from GWAS) 7 14
Heart CTOT-3 71Mb/96Mb Seq + MetaboChip ~200K to 71Mb (SGS) Imputed by IMPUTE2 at Penn State using 1KGPv3 Yes No NA 22
CTOT-5 Axiom Tx SNP GWAS array ~780K Imputed by Impute2 at UMCU and Penn state using 1KGv3 and GoNLv5 Yes No N/A 43
Stanford/LPCH Axiom Tx array + Omni 1M/2.5M ~780K Imputed by IMPUTE2 at Penn State using 1KGPv3 Yes Ad-hoc when allele specific Abs are detected 11 30
CHOP-Heart Tx Axiom Tx array + Infinium660K ~780K Imputed by Impute2 at UMCU and Penn state using 1KGv3 and GoNLv5 Yes Yes N/A 4.4
UPenn-Heart Tx Axiom Tx SNP GWAS array ~780K Imputed by IMPUTE2 at Penn State using 1KGPv3 Yes No N/A 35
UCOR Axiom Tx SNP GWAS array ~780K Imputed by Impute2 at UMCU and Penn state using 1KGv3 and GoNLv5 Yes, from 1993 No N/A 10
Madrid Heart Tx Study Axiom Tx SNP GWAS array ~780K Imputed by Impute2 at UMCU and Penn state using 1KGv3 and GoNLv5 Yes (subset) No N/A 74
Vanderbilt BioVU Infinium 660K and 1M ~660K to 1 Million Imputed by IMPUTE2 at Vanderbilt using 1KGPv3 Yes Yes, since 2006 N/A N/A
Rotterdam cohort Axiom Tx SNP GWAS array ~780K N/A Yes No N/A 62
Liver CTOT-3 71Mb + MetaboChip ~200K to 71Mb (SGS) Imputed by IMPUTE2 at Penn State using 1KGPv3 No No N/A 9
AWISH (CTOT-7) Axiom Tx SNP GWAS array ~780K Imputed by Impute2 at UMCU and Penn state using 1KGv3 and GoNLv5 No No N/A 24
A2ALL Axiom Tx SNP GWAS array ~780K Imputed by Impute2 at UMCU and Penn state using 1KGv3 and GoNLv5 No No N/A 16
CHOP-Liver Tx Axiom Tx array + Infinium660K ~780K Imputed by IMPUTE2 at Penn State using 1KGPv3 No No N/A 5
UPenn-Liver Tx Axiom Tx SNP GWAS array ~660K to 780K Imputed by IMPUTE2 at Penn State using 1KGPv3 No No N/A 11
Baylor-Liver Tx Axiom Tx SNP GWAS array ~780K Imputed by Impute2 at UMCU and Penn state using 1KGv3 and GoNLv5 Yes No 28 40
Lung LTOG Axiom Tx SNP GWAS array ~780K Imputed by IMPUTE2 at Penn State using 1KGPv3 Yes Yes 30 40
ULTx Axiom Tx SNP GWAS array ~780K Imputed by Impute2 at UMCU and Penn state using 1KGv3 and GoNLv5 Yes, prior to 1993 No 44 14
CTOT-3 71Mb + MetaboChip ~200K to 71Mb (SGS) Imputed by IMPUTE2 at Penn State using 1KGPv3 Yes No N/A 19

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