Genome-Wide Association Study Assessing Risk of Rejection in Pediatric Transplant Recipients

T. Papaz,¹ S. Min,¹ O. Lee,¹ T. Blydt-Hansen,³ U. Allen,¹ Y. Avitzur,¹ P. Birk,² B. Foster,⁴ H. Grasemann,¹ L. Hamiwka,⁵ R. Parekh,¹ V. Phan,⁶ S. Urschel,⁷ S. Mital.¹

¹SickKids Hospital, Toronto, ON, Canada
²Winnipeg Children's Hospital, Winnipeg, MB, Canada
³BC Children's Hospital, Vancouver, BC, Canada
⁴Montreal Children's Hospital, Montreal, QC, Canada
⁵Alberta Children's Hospital, Calgary, AB, Canada
⁶CHU Sainte Justines, Montreal, QC, Canada
⁷Stollery Children's Hospital, Edmonton, AB, Canada.

Meeting: 2018 American Transplant Congress

Abstract number: A444

Keywords: Genomic markers, Pediatric, Rejection

Session Information

Session Name: Poster Session A: Tolerance: Clinical Studies

Session Type: Poster Session

Date: Saturday, June 2, 2018

Session Time: 5:30pm-7:30pm

Presentation Time: 5:30pm-7:30pm

Location: Hall 4EF

Background: Rejection risk varies after solid organ transplantation (SOT). We explored genomic variants associated with susceptibility to graft rejection.

Methods: SOTs enrolled in a multicenter prospective cohort study were genotyped using the Axiom Transplant Array. Patients experiencing rejection 1-year post transplant were compared to non-rejectors. GWAS was used to assess the association of SNP with rejection risk using Cox proportional hazard and logistic regression models. 490,311 variants with a minor allele frequency of >0.01 in Hardy-Weinberg equilibrium were included. Mutation burden was performed on significant SNPs. Gene set enrichment analysis (GSEA) was used to identify gene signatures. Co-variates included were organ type, sex, age, race, ABO compatibility and induction medication use.

Results: Of 486 participants (140 renal, 153 heart, 181 liver, 12 lung), 42% experienced rejection, median time to rejection was 11.24 months. Males had a lower hazard ratio (HR) for rejection than females (HR=0.75, p<0.05), while heart and liver had a higher hazard for rejection compared to kidney recipients (p< 0.001). 20 SNPs were associated with rejection (HR range 1.64-7.95, p<10^-5). On CoxPH analysis, organ type, younger age and variant burden were associated with rejection with every additional SNP increasing risk by a HR of 1.38 (p <0.001). GSEA identified enrichment of variants in genes related to adaptive immune response, autoimmune disease, interferon signaling and regulation of autophagy.

Conclusion: Variants in immunity associated genes are associated with rejection. Clinical and genetic factors can inform the development of individualized risk prediction models for rejection.

CITATION INFORMATION: Papaz T., Min S., Lee O., Blydt-Hansen T., Allen U., Avitzur Y., Birk P., Foster B., Grasemann H., Hamiwka L., Parekh R., Phan V., Urschel S., Mital S. Genome-Wide Association Study Assessing Risk of Rejection in Pediatric Transplant Recipients Am J Transplant. 2017;17 (suppl 3).

To cite this abstract in AMA style:

Papaz T, Min S, Lee O, Blydt-Hansen T, Allen U, Avitzur Y, Birk P, Foster B, Grasemann H, Hamiwka L, Parekh R, Phan V, Urschel S, Mital S. Genome-Wide Association Study Assessing Risk of Rejection in Pediatric Transplant Recipients [abstract]. https://atcmeetingabstracts.com/abstract/genome-wide-association-study-assessing-risk-of-rejection-in-pediatric-transplant-recipients/. Accessed November 21, 2024.

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