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Weighted Genetic Risk Scores and Prediction of Weight Gain in Solid Organ Transplant Populations

Núria Saigi-Morgui, Lina Quteineh, Pierre-Yves Bochud, Severine Crettol, Zoltán Kutalik, Agnieszka Wójtowicz, Stéphanie Bibert, Sonja Beckmann, Nicolas J Mueller, Isabelle Binet, Christian Van Delden, Jürg Steiger, Paul Mohacsi, Guido Stirnimann, Paola M Soccal, Manuel Pascual, Chin B Eap &

abstract

BACKGROUND
Polygenic 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.

RESULTS
w-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.

CONCLUSIONS
This 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.
   
citation Saigi-Morgui N, Quteineh L, Bochud P Y, Crettol S, Kutalik Z, Wójtowicz A, Bibert S, Beckmann S, Mueller N J, Binet I, Van Delden C, Steiger J, Mohacsi P, Stirnimann G, Soccal P M, Pascual M, Eap C B, . Weighted Genetic Risk Scores and Prediction of Weight Gain in Solid Organ Transplant Populations. PLoS ONE 2016; 11:e0164443.
   
type journal paper/review (English)
date of publishing 27-10-2016
journal title PLoS ONE (11/10)
ISSN electronic 1932-6203
pages e0164443
PubMed 27788139
DOI 10.1371/journal.pone.0164443