title: Weighted Genetic Risk Scores and Prediction of Weight Gain in Solid Organ Transplant Populations.
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.
authors: Unit of Pharmacogenetics and Clinical Psychopharmacology, Department of Psychiatry, Lausanne University Hospital, Prilly, Switzerland.
authors: Núria
authors: N
authors: Saigi-Morgui
authors: Unit of Pharmacogenetics and Clinical Psychopharmacology, Department of Psychiatry, Lausanne University Hospital, Prilly, Switzerland.
authors: Lina
authors: L
authors: Quteineh
authors: Service of Infectious Diseases, University Hospital and University of Lausanne, Lausanne, Switzerland.
authors: Pierre-Yves
authors: PY
authors: Bochud
authors: Unit of Pharmacogenetics and Clinical Psychopharmacology, Department of Psychiatry, Lausanne University Hospital, Prilly, Switzerland.
authors: Severine
authors: S
authors: Crettol
authors: Institute of Social and Preventive Medicine (IUMSP), Lausanne University Hospital, Lausanne, Switzerland.|Swiss Institute of Bioinformatics, Lausanne, Switzerland.
authors: Zoltán
authors: Z
authors: Kutalik
authors: Service of Infectious Diseases, University Hospital and University of Lausanne, Lausanne, Switzerland.
authors: Agnieszka
authors: A
authors: Wojtowicz
authors: Service of Infectious Diseases, University Hospital and University of Lausanne, Lausanne, Switzerland.
authors: Stéphanie
authors: S
authors: Bibert
authors: Institute of Nursing Science, University of Basel, Basel, Switzerland.
authors: Sonja
authors: S
authors: Beckmann
authors: Division of Infectious Diseases and Hospital Epidemiology, University Hospital, Zurich, Switzerland.
authors: Nicolas J
authors: NJ
authors: Mueller
authors: Service of Nephrology and Transplantation Medicine, Kantonsspital, St Gallen, Switzerland.
authors: Isabelle
authors: I
authors: Binet
authors: Service of Infectious Diseases, University Hospitals, Geneva, Switzerland.
authors: Christian
authors: C
authors: van Delden
authors: Service of Nephrology, University Hospital, Basel, Switzerland.
authors: Jürg
authors: J
authors: Steiger
authors: Swiss Cardiovascular Center Bern, University Hospital, Bern, Switzerland.
authors: Paul
authors: P
authors: Mohacsi
authors: University Clinic of Visceral Surgery and Medicine, Inselspital, Bern, Switzerland.
authors: Guido
authors: G
authors: Stirnimann
authors: Service of Pulmonary Medicine, University Hospital, Geneva, Switzerland.
authors: Paola M
authors: PM
authors: Soccal
authors: Transplant Center, Lausanne University Hospital, Lausanne, Switzerland.
authors: Manuel
authors: M
authors: Pascual
authors: Unit of Pharmacogenetics and Clinical Psychopharmacology, Department of Psychiatry, Lausanne University Hospital, Prilly, Switzerland.|School of Pharmaceutical Sciences, University of Geneva, University of Lausanne, Geneva, Switzerland.
authors: Chin B
authors: CB
authors: Eap
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D015992:Body Mass Index; D005260:Female; D055106:Genome-Wide Association Study; D006085:Graft Survival / Q000235:genetics / Q000502:physiology; D006801:Humans; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000209:etiology / Q000235:genetics; D016377:Organ Transplantation / Q000009:adverse effects; D020641:Polymorphism, Single Nucleotide / Q000235:genetics* / Q000502:physiology; D012307:Risk Factors; D015430:Weight Gain / Q000235:genetics*; D055815:Young Adult