Abstract
BackgroundPolygenic obesity in Solid Organ Transplant (SOT) populations is considered a risk factor for the development of metabolic abnormalities and graft survival. Few studies to date have studied the genetics of weight gain in SOT recipients. We aimed to determine whether weighted genetic risk scores (w-GRS) integrating genetic polymorphisms from GWAS studies (SNP group#1 and SNP group#2) and from Candidate Gene studies (SNP group#3) influence BMI in SOT populations and if they predict ≥10% weight gain (WG) one year after transplantation. To do so, two samples (nA = 995, nB = 156) were obtained from naturalistic studies and three w-GRS were constructed and tested for association with BMI over time. Prediction of 10% WG at one year after transplantation was assessed with models containing genetic and clinical factors.Resultsw-GRS were associated with BMI in sample A and B combined (BMI increased by 0.14 and 0.11 units per additional risk allele in SNP group#1 and #2, respectively, p-values<0.008). w-GRS of SNP group#3 showed an effect of 0.01 kg/m2 per additional risk allele when combining sample A and B (p-value 0.04). Models with genetic factors performed better than models without in predicting 10% WG at one year after transplantation.ConclusionsThis is the first study in SOT evaluating extensively the association of w-GRS with BMI and the influence of clinical and genetic factors on 10% of WG one year after transplantation, showing the importance of integrating genetic factors in the final model. Genetics of obesity among SOT recipients remains an important issue and can contribute to treatment personalization and prediction of WG after transplantation.
Highlights
Obesity has become a worldwide major concern since it has more than doubled in the last decades
This does not alter our adherence to PLOS ONE policies on sharing data and materials. This is the first study in Solid Organ Transplant (SOT) evaluating extensively the association of weighted genetic risk scores (w-GRS) with BMI and the influence of clinical and genetic factors on 10% of weight gain (WG) one year after transplantation, showing the importance of integrating genetic factors in the final model
Obesity in SOT is an important risk factor for the development of New Onset Diabetes after Transplant (NODAT) [6] which has a deleterious effect on graft survival [7, 8]
Summary
Obesity has become a worldwide major concern since it has more than doubled in the last decades. Obesity in SOT is an important risk factor for the development of New Onset Diabetes after Transplant (NODAT) [6] which has a deleterious effect on graft survival [7, 8]. It can be often associated with delayed graft function related to surgical and post-operative complications [9]. Polygenic obesity in Solid Organ Transplant (SOT) populations is considered a risk factor for the development of metabolic abnormalities and graft survival. Prediction of 10% WG at one year after transplantation was assessed with models containing genetic and clinical factors
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