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

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.

SUBMITTER: Dos Santos Q

PROVIDER: S-EPMC10733470 | biostudies-literature | 2023

REPOSITORIES: biostudies-literature

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

Dos Santos Quenia Q Leung Preston P Thorball Christian W CW Ledergerber Bruno B Fellay Jacques J MacPherson Cameron R CR Hornum Mads M Terrones-Campos Cynthia C Rasmussen Allan A Gustafsson Finn F Perch Michael M Sørensen Søren S SS Ekenberg Christina C Lundgren Jens D JD Feldt-Rasmussen Bo B Reekie Joanne J

Frontiers in molecular biosciences 20231207

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-transpl ...[more]

PMID: 38131015

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Project description:ContextAnxiety disorders are common, with a lifetime prevalence of 20% in the U.S., and are responsible for substantial burdens of disability, missed work days and health care utilization. To date, no causal genetic variants have been identified for anxiety, anxiety disorders, or related traits.ObjectiveTo investigate whether a phobic anxiety symptom score was associated with 3 alternative polygenic risk scores, derived from external genome-wide association studies of anxiety, an internally estimated agnostic polygenic score, or previously identified candidate genes.DesignLongitudinal follow-up study. Using linear and logistic regression we investigated whether phobic anxiety was associated with polygenic risk scores derived from internal, leave-one out genome-wide association studies, from 31 candidate genes, and from out-of-sample genome-wide association weights previously shown to predict depression and anxiety in another cohort.Setting and participantsStudy participants (n?=?11,127) were individuals from the Nurses' Health Study and Health Professionals Follow-up Study.Main outcome measureAnxiety symptoms were assessed via the 8-item phobic anxiety scale of the Crown Crisp Index at two time points, from which a continuous phenotype score was derived.ResultsWe found no genome-wide significant associations with phobic anxiety. Phobic anxiety was also not associated with a polygenic risk score derived from the genome-wide association study beta weights using liberal p-value thresholds; with a previously published genome-wide polygenic score; or with a candidate gene risk score based on 31 genes previously hypothesized to predict anxiety.ConclusionThere is a substantial gap between twin-study heritability estimates of anxiety disorders ranging between 20-40% and heritability explained by genome-wide association results. New approaches such as improved genome imputations, application of gene expression and biological pathways information, and incorporating social or environmental modifiers of genetic risks may be necessary to identify significant genetic predictors of anxiety.

Project description:BackgroundA machine-learning approach identified five subgroups of diabetes in Europeans which included severe autoimmune diabetes (SAID), severe insulin-deficient diabetes (SIDD), severe insulin-resistant diabetes (SIRD), mild obesity-related diabetes (MOD) and mild age-related diabetes (MARD) with partially distinct genetic aetiologies. We previously validated four of the non-autoimmune subgroups in people with young-onset type 2 diabetes (T2D) from the Indian WellGen study. Here, we aimed to apply European-derived centroids and genetic risk scores (GRSs) to the unselected (for age) WellGen to test their applicability and investigate the genetic aetiology of the Indian T2D subgroups.MethodsWe applied European derived centroids and GRSs to T2D participants of Indian ancestry (WellGen, n = 2217, 821 genotyped) and compared them with normal glucose tolerant controls (Pune Maternal Nutrition Study, n = 461).FindingsSIDD was the predominant subgroup followed by MOD, whereas SIRD and MARD were less frequent. Weighted-GRS for T2D, obesity and lipid-related traits associated with T2D. We replicated some of the previous associations of GRS for T2D, insulin secretion, and BMI with SIDD and MOD. Unique to Indian subgroups was the association of GRS for (a) proinsulin with MOD and MARD, (b) liver-lipids with SIDD, SIRD and MOD, and (c) opposite effect of beta-cell GRS with SIDD and MARD, obesity GRS with MARD compared to Europeans. Genetic variants of fucosyltransferases were associated with T2D and MOD in Indians but not Europeans.InterpretationThe similarities emphasise the applicability of some of the European-derived GRSs to T2D and its subgroups in India while the differences highlight the need for large-scale studies to identify aetiologies in diverse ancestries. The data provide robust evidence for genetically distinct aetiologies for the T2D subgroups and at least partly mirror those seen in Europeans.FundingVetenskapsrådet, Diabetes Wellness, and Hjärt-Lungfonden (Sweden), DST (India), Wellcome Trust, Crafoord Foundation and Albert Påhlsson Foundation.

Project description:IntroductionPsychosocial distress and mental health problems are common in patients before and after solid organ transplantation and can negatively affect morbidity, mortality, and adherence. Even though regular screening is recommended to identify patients with high levels of distress, the implementation in routine care has been insufficient so far.MethodsTwo newly developed problem lists for patients before and after transplantations were pilot implemented for 8 weeks at the Medical Center Hamburg Eppendorf (UKE) to identify factors facilitating and impeding their implementation.ResultsHealth care professionals evaluated its appropriateness, feasibility, and the cooperation with the psychologists before (HCPs: n = 23) and after (HCPs: n = 19) the implementation. Four psychologists assessed the appropriateness and feasibility by answering to open-ended and close-ended questions. Additionally, patients before (n = 8) and after (n = 100) transplantation filled out the screening and rated its acceptance. Only the data of the patients after transplantation were analyzed due to the small sample size of patients before transplantation. HCPs and psychologists rated the screenings as very appropriate [HCPs: M = 3.84 (SD = 0.77) to M = 4.32 (SD = 0.58)]. It was also highly accepted among patients [M = 4.23 (SD = 0.85) to M = 4.68 (SD = 0.65)]. Contentment with the psychological support and understanding of the mental health problems among HCPs increased significantly from before to after the implementation (U = 107.50, p < 0.05, r = 0.33; U = 107.00, p < 0.05, r = 0.34). The feasibility of the problem list post-Tx in routine care, however, was seen as challenging [HCPs: M = 3.11 (SD = 1.05) to M = 3.47 (SD = 1.07)].DiscussionThe distress screening was accepted and improved the cooperation between different professions. Barriers to implementation can be lack of staff and resources. Future studies should assess the adoption and sustainability of the screening in routine care.

Dataset Information

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

Publications

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

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