Korean J Transplant.
2023 Nov;37(Suppl 1):S116. 10.4285/ATW2023.F-7003.
Unveiling shared genetic risks of type 2 and posttransplant diabetes mellitus in East Asians through polygenic risk scores
- Affiliations
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- 1Department of Nephrology, Seoul National University Bundang Hospital, Seongnam, Korea
- 2Department of Precision Medicine, National Institute of Health, Osong, Korea
- 3Department of Nephrology, Severance Hospital, Yonsei University, Seoul, Korea
- 4Department of Surgery, Severance Hospital, Yonsei University, Seoul, Korea
- 5National Institute of Health, Osong, Korea
- KMID: 2551736
- DOI: http://doi.org/10.4285/ATW2023.F-7003
Abstract
- Background
Posttransplant diabetes mellitus (PTDM) contributes to adverse cardiovascular outcomes in kidney transplant recipients (KTRs). We examined whether polygenic risk scores (PRSs) for type 2 diabetes mellitus (T2D) can predict PTDM in an East Asian cohort. Further, partitioned T2D PRSs representing distinct clusters of cardiometabolic traits were utilized to investigate whether PTDM exhibits unique associations.
Methods
We constructed T2D PRSs with genome-wide association study (GWAS) data from BioBank Japan (PRSBBJ) and from the East Asian (PRSEastAsian) and Trans-ethnic (PRSTrans) components of the Diabetes Meta-Analysis of Trans-Ethnic association studies. The performances of the T2D PRSs were validated in the general population (T2D, n=12,983; control, n=101,267) from the Korean Genome Epidemiology Study (KoGES). We devised a PTDM PRS (PRSPTDM) with the previous PTDM GWAS by McCaughan et al. The associations of the PRSs and PTDM development were explored in 1,524 KTRs including 190 PTDM cases from the Korean Organ Transplantation Registry. We further acquired another set of T2D PRSs based on eight mechanistic clusters from the largest T2D multi-ancestry GWAS meta-analysis to date by Suzuki et al. 2023. We compared the associations of the mechanism-specific PRSs with T2D and PTDM to understand possible genetic discrepancy. Genotyping was performed using the Korea Biobank Array.
Results
PRSBBJ, PRSEastAsian, and PRSTrans were externally validated to predict T2D using logistic regressions, with Nagelkerke pseudo-R2 values of 0.088, 0.083, and 0.087, respectively. Cox regressions demonstrated that PRSBBJ (hazard ratio [HR], 1.60; P=1.08×10–10), PRSEastAsian (HR, 1.58; P=2.29×10–10), and PRSTrans (HR, 1.56; P=7.04×10–10) were significantly associated with the PTDM development. PRSPTDM (HR, 1.00; P=0.954) failed to predict PTDM, possibly due to the limited number of variants. Incident T2D from the KoGES and PTDM showed similar associations with mechanism-specific PRSs.
Conclusions
T2D PRS can stratify PTDM risks. Thorough PRS analyses suggest shared genetic mechanisms between T2D and PTDM.
