The impact of donor and recipient common clinical and genetic variation on estimated glomerular filtration rate in a European renal transplant population. Issue 8 (28th March 2019)

• Record Type: Journal Article
• Authors: Stapleton, Caragh P.; Heinzel, Andreas; Guan, Weihua; van der Most, Peter J.; van Setten, Jessica; Lord, Graham M.; Keating, Brendan J.; Israni, Ajay K.; de Borst, Martin H.; Bakker, Stephan J. L.; Snieder, Harold; Weale, Michael E.; Delaney, Florence; Hernandez‐Fuentes, Maria P.; Reindl‐Schwaighofer, Roman; Oberbauer, Rainer; Jacobson, Pamala A.; Mark, Patrick B.; Chapman, Fiona A.; Phelan, Paul J.; Kennedy, Claire; Sexton, Donal; Murray, Susan; Jardine, Alan; Traynor, Jamie P.; McKnight, Amy Jayne; Maxwell, Alexander P.; Smyth, Laura J.; Oetting, William S.; Matas, Arthur J.; Mannon, Roslyn B.; Schladt, David P.; Iklé, David N.; Cavalleri, Gianpiero L.; Conlon, Peter J.;
• Other Names: Franklin Christopher investigator.; Rebollo‐Mesa Irene investigator.; Mollon Jennifer investigator.; Perucha Esperanza investigator.; Borrows Richard investigator.; Byrne Catherine investigator.; Clarke Brendan investigator.; Clatworthy Menna investigator.; Feehally John investigator.; Fuggle Susan investigator.; Gagliano Sarah A. investigator.; Griffin Sian investigator.; Hammad Abdul investigator.; Higgins Robert investigator.; Keogan Mary investigator.; Leach Timothy investigator.; MacPhee Iain investigator.; Marsh James investigator.; Maxwell Peter investigator.; McKane William investigator.; McLean Adam investigator.; Newstead Charles investigator.; Augustine Titus investigator.; Powis Steve investigator.; Rowe Peter investigator.; Sheerin Neil investigator.; Solomon Ellen investigator.; Stephens Henry investigator.; Thuraisingham Raj investigator.; Trembath Richard investigator.; Topham Peter investigator.; Vaughan Robert investigator.; Sacks Steven H. investigator.; Opelz Gerhard investigator.; Soranzo Nicole investigator.; Cecka J. Michael investigator.; Connett John investigator.; Cosio Fernando G. investigator.; Gaston Robert investigator.; Gourishankar Sita investigator.; Grande Joseph P. investigator.; Hunsicker Lawrence investigator.; Kasiske Bertram investigator.; Rush David investigator.;
• Is Part Of: American journal of transplantation. Volume 19:Issue 8(2019)
• Page Start: 2262
• Page End: 2273
• Publication Date: 2019-03-28
• Subjects: basic (laboratory) research/science -- clinical research/practice -- genetics -- genomics -- glomerular filtration rate (GFR) -- kidney transplantation/nephrology -- microarray/gene array -- molecular biology: DNA; Transplantation of organs, tissues, etc -- Periodicals; 617.95
• DOI: 10.1111/ajt.15326
• Languages: English
• ISSNs: 1600-6135

Abstract

Abstract : Genetic variation across the human leukocyte antigen loci is known to influence renal‐transplant outcome. However, the impact of genetic variation beyond the human leukocyte antigen loci is less clear. We tested the association of common genetic variation and clinical characteristics, from both the donor and recipient, with posttransplant eGFR at different time‐points, out to 5 years posttransplantation. We conducted GWAS meta‐analyses across 10 844 donors and recipients from five European ancestry cohorts. We also analyzed the impact of polygenic risk scores (PRS), calculated using genetic variants associated with nontransplant eGFR, on posttransplant eGFR. PRS calculated using the recipient genotype alone, as well as combined donor and recipient genotypes were significantly associated with eGFR at 1‐year posttransplant. Thirty‐two percent of the variability in eGFR at 1‐year posttransplant was explained by our model containing clinical covariates (including weights for death/graft‐failure), principal components and combined donor‐recipient PRS, with 0.3% contributed by the PRS. No individual genetic variant was significantly associated with eGFR posttransplant in the GWAS. This is the first study to examine PRS, composed of variants that impact kidney function in the general population, in a posttransplant context. Despite PRS being a significant predictor of eGFR posttransplant, the effect size of common genetic factors is limited compared to clinical variables. Abstract : Polygenic risk score of nontransplant eGFR is a significant predictor of eGFR at 1 year posttransplant, but the effect size contributed by these common genetic variants is limited compared to that of clinical variables.