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The genomics of transplant-related outcomes and familial renal disease

posted on 05.08.2020 by Caragh Stapleton
Chronic kidney disease (CKD) is a growing global health concern with an age-standardized global prevalence of approximately 10%. Of those with CKD, approximately 2% will go on to require renal replacement therapy within any given 5-year period. Renal transplantation is accepted as the most clinically- and cost-effective treatment for end-stage kidney failure. In this thesis, we set out to examine the impact of common genetic variation on renal transplant function as well as a common post-transplant complication: non-melanoma skin cancer. We also aimed to examine a common form of CKD, IgA nephropathy, in a familial context using next generation sequencing techniques. We demonstrated that polygenic (but not single variant) effects of common genetic variation found in both the kidney donor and recipient impacts the function of the renal allograft in the early stages post-transplant. We also illustrated how measures of post-transplant renal outcomes do not correlate with the level of shared genetic ancestry between unrelated kidney donors and recipients in a cohort of European, deceased-donor transplants. We also showed that polygenic (but not single variant) effects of common genetic variation impacts both whether or not an individual develops post-transplant non-melanoma skin cancer but also, the speed at which they develop non-melanoma skin cancer. Finally, in our exome sequencing analysis of familial IgAN, we found that a number of Irish families carried rare, damaging and potentially disease-causing mutations in type IV collagen-related genes, known to cause kidney disease. In summary, this thesis demonstrates the impact of genetic variation on both kidney disease and transplant outcomes.


First Supervisor

Professor Gianpiero L. Cavalleri

Second Supervisor

Professor Peter J. Conlon


A thesis submitted for the degree of Doctor of Philosophy from the Royal College of Surgeons in Ireland in 2019.

Published Citation

Stapleton C. The genomics of transplant-related outcomes and familial renal disease. [PhD Thesis]. Dublin: Royal College of Surgeons in Ireland; 2019.

Degree Name

Doctor of Philosophy (PhD)

Date of award



  • Doctor of Philosophy (PhD)


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