AUTHOR=dos Santos Quenia , Leung Preston , Thorball Christian W. , Ledergerber Bruno , Fellay Jacques , MacPherson Cameron R. , Hornum Mads , Terrones-Campos Cynthia , Rasmussen Allan , Gustafsson Finn , Perch Michael , Sørensen Søren S. , Ekenberg Christina , Lundgren Jens D. , Feldt‐Rasmussen Bo , Reekie Joanne TITLE=Predicting type 2 diabetes risk before and after solid organ transplantation using polygenic scores in a Danish cohort JOURNAL=Frontiers in Molecular Biosciences VOLUME=10 YEAR=2023 URL=https://www.frontiersin.org/journals/molecular-biosciences/articles/10.3389/fmolb.2023.1282412 DOI=10.3389/fmolb.2023.1282412 ISSN=2296-889X ABSTRACT=

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.