Longitudinal epigenome-wide analysis of kidney transplant recipients pretransplant and posttransplant

Laura J.  Smyth; Katie R. Kerr; Jill Kilner; Áine E. McGill; Alexander P.  Maxwell; Amy Jayne McKnight

doi:10.1016/j.ekir.2022.11.001

Longitudinal epigenome-wide analysis of kidney transplant recipients pretransplant and posttransplant

Laura J. Smyth, Katie R. Kerr, Jill Kilner, Áine E. McGill, Alexander P. Maxwell, Amy Jayne McKnight^*

^*Corresponding author for this work

School of Medicine, Dentistry and Biomedical Sciences

Research output: Contribution to journal › Article › peer-review

6 Citations (Scopus)

79 Downloads (Pure)

Abstract

Introduction

Kidney transplantation remains the gold standard of treatment for end-stage renal disease (ESRD), with improved patient outcomes compared with dialysis. Epigenome-Wide Association Analysis (EWAS) of DNA methylation may identify markers that contribute to an individual's risk of adverse transplant outcomes, yet only a limited number of EWAS have been conducted in kidney transplant recipients. This EWAS aimed to interrogate the methylation profile of a kidney transplant recipient cohort with minimal posttransplant complications, exploring differences in samples pretransplant and posttransplant.

Methods

We compared differentially methylated cytosine-phosphate-guanine sites (dmCpGs) in samples derived from peripheral blood mononuclear cells of the same kidney transplant recipients, collected both pretransplant and posttransplant (N = 154), using the Infinium MethylationEPIC microarray (Illumina, San Diego, CA). Recipients received kidneys from deceased donors and had a mean of 17 years of follow-up.

Results

Five top-ranked dmCpGs were significantly different at false discovery rate (FDR) adjusted P ≤ 9 × 10^-8; cg23597162 within JAZF1, cg25187293 within BTNL8, cg17944885, located between ZNF788P and ZNF625-ZNF20, cg14655917 located between ASB4 and PDK4 and cg09839120 located between GIMAP6 and EIF2AP3.

Conclusion

Five dmCpGs were identified at the generally accepted EWAS critical significance level of FDR adjusted P (P _FDRadj) ≤ 9 × 10^-8, including cg23597162 (within JAZF1) and cg17944885, which have prior associations with chronic kidney disease (CKD). Comparing individuals with no evidence of posttransplant complications (N = 105) demonstrated that 693,555 CpGs (89.57%) did not display any significant difference in methylation (P _FDRadj ≥ 0.05), thereby this study establishes an important reference for future epigenetic studies that seek to identify markers of posttransplant complications.

Original language	English
Pages (from-to)	330-340
Number of pages	11
Journal	Kidney International Reports
Volume	8
Issue number	2
DOIs	https://doi.org/10.1016/j.ekir.2022.11.001
Publication status	Published - 01 Feb 2023

Bibliographical note

This document is associated with an editorial, "Epigenome-wide association studies of DNA methylation in kidney diseases": https://www.kireports.org/article/S2468-0249(22)01885-X/fulltext

Keywords

kidney
methylation
transplant
rare
Epigenetic

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1016/j.ekir.2022.11.001Licence: CC BY-NC-ND

Longitudinal epigenome-wide analysis of kidney transplant recipients pretransplant and posttransplant
Copyright 2022 International Society of Nephrology. This is an open access article published under a Creative Commons Attribution-NonCommercial-NoDerivs License (https://creativecommons.org/licenses/by-nc-nd/4.0/), which permits distribution and reproduction for non-commercial purposes, provided the author and source are cited.
Final published version, 455 KBLicence: CC BY-NC-ND

R4015CPH: Social Circumstances and Epigenomics Promoting Health in Three Countries
McKnight, A. J. (PI), Cruise, S. (CoI), Kee, F. (CoI) & McGuinness, B. (CoI)
06/11/2020 → …
Project: Research
R3789CPH: Discovery of an integrated risk profile for chronic kidney disease and development of a clinical biomarker panel for personalising medicine (Stratified medicine for chronic kidney disease)
McKnight, A. J. (PI) & Maxwell, P. (CoI)
15/06/2016 → …
Project: Research

Determining effective radiation / drug combinations for paediatric cancers
McGill, A. (Author), Prise, K. (Supervisor) & Mills, K. (Supervisor), Jul 2024
Student thesis: Doctoral Thesis › Doctor of Philosophy

Cite this

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title = "Longitudinal epigenome-wide analysis of kidney transplant recipients pretransplant and posttransplant",

abstract = "IntroductionKidney transplantation remains the gold standard of treatment for end-stage renal disease (ESRD), with improved patient outcomes compared with dialysis. Epigenome-Wide Association Analysis (EWAS) of DNA methylation may identify markers that contribute to an individual's risk of adverse transplant outcomes, yet only a limited number of EWAS have been conducted in kidney transplant recipients. This EWAS aimed to interrogate the methylation profile of a kidney transplant recipient cohort with minimal posttransplant complications, exploring differences in samples pretransplant and posttransplant.MethodsWe compared differentially methylated cytosine-phosphate-guanine sites (dmCpGs) in samples derived from peripheral blood mononuclear cells of the same kidney transplant recipients, collected both pretransplant and posttransplant (N = 154), using the Infinium MethylationEPIC microarray (Illumina, San Diego, CA). Recipients received kidneys from deceased donors and had a mean of 17 years of follow-up.ResultsFive top-ranked dmCpGs were significantly different at false discovery rate (FDR) adjusted P ≤ 9 × 10-8; cg23597162 within JAZF1, cg25187293 within BTNL8, cg17944885, located between ZNF788P and ZNF625-ZNF20, cg14655917 located between ASB4 and PDK4 and cg09839120 located between GIMAP6 and EIF2AP3.ConclusionFive dmCpGs were identified at the generally accepted EWAS critical significance level of FDR adjusted P (P FDRadj) ≤ 9 × 10-8, including cg23597162 (within JAZF1) and cg17944885, which have prior associations with chronic kidney disease (CKD). Comparing individuals with no evidence of posttransplant complications (N = 105) demonstrated that 693,555 CpGs (89.57%) did not display any significant difference in methylation (P FDRadj ≥ 0.05), thereby this study establishes an important reference for future epigenetic studies that seek to identify markers of posttransplant complications.",

keywords = "kidney, methylation, transplant, rare, Epigenetic",

author = "Smyth, {Laura J.} and Kerr, {Katie R.} and Jill Kilner and McGill, {{\'A}ine E.} and Maxwell, {Alexander P.} and McKnight, {Amy Jayne}",

note = "This document is associated with an editorial, {"}Epigenome-wide association studies of DNA methylation in kidney diseases{"}: https://www.kireports.org/article/S2468-0249(22)01885-X/fulltext",

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doi = "10.1016/j.ekir.2022.11.001",

language = "English",

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T1 - Longitudinal epigenome-wide analysis of kidney transplant recipients pretransplant and posttransplant

AU - Smyth, Laura J.

AU - Kerr, Katie R.

AU - Kilner, Jill

AU - McGill, Áine E.

AU - Maxwell, Alexander P.

AU - McKnight, Amy Jayne

N1 - This document is associated with an editorial, "Epigenome-wide association studies of DNA methylation in kidney diseases": https://www.kireports.org/article/S2468-0249(22)01885-X/fulltext

PY - 2023/2/1

Y1 - 2023/2/1

N2 - IntroductionKidney transplantation remains the gold standard of treatment for end-stage renal disease (ESRD), with improved patient outcomes compared with dialysis. Epigenome-Wide Association Analysis (EWAS) of DNA methylation may identify markers that contribute to an individual's risk of adverse transplant outcomes, yet only a limited number of EWAS have been conducted in kidney transplant recipients. This EWAS aimed to interrogate the methylation profile of a kidney transplant recipient cohort with minimal posttransplant complications, exploring differences in samples pretransplant and posttransplant.MethodsWe compared differentially methylated cytosine-phosphate-guanine sites (dmCpGs) in samples derived from peripheral blood mononuclear cells of the same kidney transplant recipients, collected both pretransplant and posttransplant (N = 154), using the Infinium MethylationEPIC microarray (Illumina, San Diego, CA). Recipients received kidneys from deceased donors and had a mean of 17 years of follow-up.ResultsFive top-ranked dmCpGs were significantly different at false discovery rate (FDR) adjusted P ≤ 9 × 10-8; cg23597162 within JAZF1, cg25187293 within BTNL8, cg17944885, located between ZNF788P and ZNF625-ZNF20, cg14655917 located between ASB4 and PDK4 and cg09839120 located between GIMAP6 and EIF2AP3.ConclusionFive dmCpGs were identified at the generally accepted EWAS critical significance level of FDR adjusted P (P FDRadj) ≤ 9 × 10-8, including cg23597162 (within JAZF1) and cg17944885, which have prior associations with chronic kidney disease (CKD). Comparing individuals with no evidence of posttransplant complications (N = 105) demonstrated that 693,555 CpGs (89.57%) did not display any significant difference in methylation (P FDRadj ≥ 0.05), thereby this study establishes an important reference for future epigenetic studies that seek to identify markers of posttransplant complications.

AB - IntroductionKidney transplantation remains the gold standard of treatment for end-stage renal disease (ESRD), with improved patient outcomes compared with dialysis. Epigenome-Wide Association Analysis (EWAS) of DNA methylation may identify markers that contribute to an individual's risk of adverse transplant outcomes, yet only a limited number of EWAS have been conducted in kidney transplant recipients. This EWAS aimed to interrogate the methylation profile of a kidney transplant recipient cohort with minimal posttransplant complications, exploring differences in samples pretransplant and posttransplant.MethodsWe compared differentially methylated cytosine-phosphate-guanine sites (dmCpGs) in samples derived from peripheral blood mononuclear cells of the same kidney transplant recipients, collected both pretransplant and posttransplant (N = 154), using the Infinium MethylationEPIC microarray (Illumina, San Diego, CA). Recipients received kidneys from deceased donors and had a mean of 17 years of follow-up.ResultsFive top-ranked dmCpGs were significantly different at false discovery rate (FDR) adjusted P ≤ 9 × 10-8; cg23597162 within JAZF1, cg25187293 within BTNL8, cg17944885, located between ZNF788P and ZNF625-ZNF20, cg14655917 located between ASB4 and PDK4 and cg09839120 located between GIMAP6 and EIF2AP3.ConclusionFive dmCpGs were identified at the generally accepted EWAS critical significance level of FDR adjusted P (P FDRadj) ≤ 9 × 10-8, including cg23597162 (within JAZF1) and cg17944885, which have prior associations with chronic kidney disease (CKD). Comparing individuals with no evidence of posttransplant complications (N = 105) demonstrated that 693,555 CpGs (89.57%) did not display any significant difference in methylation (P FDRadj ≥ 0.05), thereby this study establishes an important reference for future epigenetic studies that seek to identify markers of posttransplant complications.

KW - kidney

KW - methylation

KW - transplant

KW - rare

KW - Epigenetic

U2 - 10.1016/j.ekir.2022.11.001

DO - 10.1016/j.ekir.2022.11.001

M3 - Article

SN - 2468-0249

VL - 8

SP - 330

EP - 340

JO - Kidney International Reports

JF - Kidney International Reports

IS - 2

ER -

Longitudinal epigenome-wide analysis of kidney transplant recipients pretransplant and posttransplant

Abstract

Introduction

Methods

Results

Conclusion

Bibliographical note

Keywords

UN SDGs

Access to Document

Fingerprint

Projects

R4015CPH: Social Circumstances and Epigenomics Promoting Health in Three Countries

R3789CPH: Discovery of an integrated risk profile for chronic kidney disease and development of a clinical biomarker panel for personalising medicine (Stratified medicine for chronic kidney disease)

Student theses

Determining effective radiation / drug combinations for paediatric cancers

Cite this