iGeneTRAiN – an Overview

Tens of millions of individuals worldwide, suffer from end-stage diseases and congenital conditions, for which the only treatment is transplantation. Over 833,000 transplants were performed in the US over the last five decades In 2018, there were a total of around 146,840 organ transplants worldwide. Unfortunately, the availability of donor organs has not kept pace with demand and 108,000 people are on the waiting list for an organ in the US as of Dec 2020.

Major advancements in organ preservation and drugs to suppress the immune system have advanced patient survival. But there are still major issues with the rejection of the transplanted organs and immunosuppression drugs. Scientists in the field of human genomics are making significant breakthroughs. Genomic tools have unveiled thousands of discoveries of specific genes and polymorphisms in every major disease area, typically by combining similar studies across different study sites. Many of these genetic discoveries are leading to new drug targets, repositioning of existing drugs, interventional treatments, and even cures.

In typical unrelated transplantation, ~3.5 million to 10 million genetic variants are observed between a donor and a recipient’s genomes. Certain regions of the genome, such as the ‘HLA’ and ‘KIR’ regions are known to impact transplant outcomes. Our knowledge of the impact around these key regions and across the genome is still in its infancy as there are very few single transplant genomic studies with sufficient numbers of subjects to discover relevant genetic signals. There is a compelling need for combining well-characterized studies to increase the statistical power to discover these new genetic regions. The International Genetics & Translational Research in Transplantation Network (iGeneTRAiN) has brought together the major transplant genetic studies conducted to date. It now encompasses over 56,000 samples from over a dozen countries with approximately 800,000 million genetic variants scanned across the genomes of these individuals.

iGeneTRAiN is currently combining genetic data from these subjects with the aim of detecting genes and specific variants underpinning rejection. A number of the iGeneTRAiN studies are also working on markers from urine, blood, and tissue to predict rejection weeks to months before it manifests clinically.

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