Current opinion in organ transplantation · 2026
GWAS studies and polygenic risk scores in organ transplantation.
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Stimmeder Sabrina, Festen Eleonora A M, de Meijer Vincent E
Аннотация
PURPOSE OF REVIEW: To summarize recent developments published between 1 January 2024 and 15 August 2026 in genome-wide and polygenic analyses of solid organ transplantation, with a focus on kidney, heart, liver, and lung transplantation.
RECENT FINDINGS: Recent studies demonstrate that posttransplant phenotypes can reflect distinct genetic contributions from the recipient, donor organ, and donor-recipient pair. Donor and recipient polygenic risk scores have been associated with graft function, graft survival, and posttransplant complications, although their incremental predictive value beyond clinical factors has generally been modest. Genome-wide analyses of donor-recipient mismatch have identified genetic differences outside the HLA region associated with rejection and graft loss. Emerging evidence suggests that the biological relevance of mismatch depends not only on the extent of genetic difference, but also on its functional nature and direction. However, most studies remain limited by small, highly selected cohorts, limited independent replication, and predominant European ancestry.
SUMMARY: Genome-wide and polygenic approaches are expanding the conceptual framework of transplant genetics beyond individual variants and HLA matching. Current evidence provides stronger support for biological relevance than clinical utility. Larger, diverse, and deeply phenotyped donor-recipient cohorts are needed to determine whether genome-wide genetic measures can improve posttransplant risk prediction and donor-recipient matching.
RECENT FINDINGS: Recent studies demonstrate that posttransplant phenotypes can reflect distinct genetic contributions from the recipient, donor organ, and donor-recipient pair. Donor and recipient polygenic risk scores have been associated with graft function, graft survival, and posttransplant complications, although their incremental predictive value beyond clinical factors has generally been modest. Genome-wide analyses of donor-recipient mismatch have identified genetic differences outside the HLA region associated with rejection and graft loss. Emerging evidence suggests that the biological relevance of mismatch depends not only on the extent of genetic difference, but also on its functional nature and direction. However, most studies remain limited by small, highly selected cohorts, limited independent replication, and predominant European ancestry.
SUMMARY: Genome-wide and polygenic approaches are expanding the conceptual framework of transplant genetics beyond individual variants and HLA matching. Current evidence provides stronger support for biological relevance than clinical utility. Larger, diverse, and deeply phenotyped donor-recipient cohorts are needed to determine whether genome-wide genetic measures can improve posttransplant risk prediction and donor-recipient matching.