Frontiers in Molecular Biosciences (Dec 2023)

Predicting type 2 diabetes risk before and after solid organ transplantation using polygenic scores in a Danish cohort

  • Quenia dos Santos,
  • Preston Leung,
  • Christian W. Thorball,
  • Christian W. Thorball,
  • Bruno Ledergerber,
  • Jacques Fellay,
  • Jacques Fellay,
  • Cameron R. MacPherson,
  • Cameron R. MacPherson,
  • Mads Hornum,
  • Cynthia Terrones-Campos,
  • Allan Rasmussen,
  • Finn Gustafsson,
  • Finn Gustafsson,
  • Michael Perch,
  • Michael Perch,
  • Søren S. Sørensen,
  • Christina Ekenberg,
  • Jens D. Lundgren,
  • Bo Feldt‐Rasmussen,
  • Joanne Reekie

DOI
https://doi.org/10.3389/fmolb.2023.1282412
Journal volume & issue
Vol. 10

Abstract

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Type 2 diabetes mellitus (T2DM) can be multifactorial where both genetics and environmental factors play a role. We aimed to investigate the use of polygenic risk scores (PRS) in the prediction of pre-transplant T2DM and post-transplant diabetes mellitus (PTDM) among solid organ transplant (SOT) patients. Using non-genetic risk scores alone; and the combination with PRS, separate logistic regression models were built and compared using receiver operator curves. Patients were assessed pre-transplant and in three post-transplant periods: 0–45, 46–365 and >365 days. A higher PRS was significantly associated with increased odds of pre-transplant T2DM. However, no improvement was observed for pre-transplant T2DM prediction when comparing PRS combined with non-genetic risk scores to using non-genetic risk scores alone. This was also true for predictions of PTDM in all three post-transplant periods. This study demonstrated that polygenic risk was only associated with the risk of T2DM among SOT recipients prior to transplant and not for PTDM. Combining PRS with a clinical model of non-genetic risk scores did not significantly improve the predictive ability, indicating its limited clinical utility in identifying patients at high risk for T2DM before transplantation, suggesting that non-genetic or different genetic factors may contribute to PTDM.

Keywords