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

Publication

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

Journal Paper/Review - Oct 27, 2016

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

Citation

Saigi-Morgui N, Eap C, Pascual M, Soccal P, Stirnimann G, Mohacsi P, Steiger J, Van Delden C, Binet F, Mueller N, Beckmann S, Bibert S, Wójtowicz A, Kutalik Z, Crettol S, Bochud P, Quteineh L. Weighted Genetic Risk Scores and Prediction of Weight Gain in Solid Organ Transplant Populations. PloS one 2016; 11:e0164443.

Type

Journal Paper/Review (English)

Journal

PloS one 2016; 11

Publication Date

Oct 27, 2016

Issn Electronic

1932-6203

Pages

e0164443

Brief description/objective

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.