title: A Genetic Risk Score Is Associated with Weight Loss Following Roux-en Y Gastric Bypass Surgery.
abstract: Currently, Roux-en Y gastric bypass (RYGB) is the most efficient therapy for severe obesity. Weight loss after surgery is, however, highly variable and genetically influenced. Genome-wide association studies have identified several single nucleotide polymorphisms (SNP) associated with body mass index (BMI) and waist-hip ratio (WHR). We aimed to identify two genetic risk scores (GRS) composed of weighted BMI and WHR-associated SNPs to estimate their impact on excess BMI loss (EBMIL) after RYGB surgery.
  
  
  
  Two hundred and thirty-eight obese patients (BMI 45.1 ± 6.2 kg/m(2), 74 % women), who underwent RYGB, were genotyped for 35 BMI and WHR-associated SNPs and were followed up after 2 years. SNPs with high impact on post-surgical weight loss were filtered out using a random forest model. The filtered SNPs were combined into a GRS and analyzed in a linear regression model.
  
  
  
  An up to 11 % lower EBMIL with higher risk score was estimated for two GRS models (P = 0.026 resp. P = 0.021) composed of seven BMI-associated SNPs (closest genes: MC4R, TMEM160, PTBP2, NUDT3, TFAP2B, ZNF608, MAP2K5, GNPDA2, and MTCH2) and of three WHR-associated SNPs (closest genes: HOXC13, LYPLAL1, and DNM3-PIGC). Patients within the lowest GRS quartile had higher EBMIL compared to patients within the other three quartiles in both models.
  
  
  
  We identified two GRSs composed of BMI and WHR-associated SNPs with significant impact on weight loss after RYGB surgery using random forest analysis as a SNP selection tool. The GRS may be useful to pre-surgically evaluate the risks for patients undergoing RYGB surgery.
authors.affiliation: Department of Neuroscience, Functional Pharmacology, Uppsala University, Box 593, 751 24, Uppsala, Sweden. marcus.bandstein@neuro.uu.se.
authors.forename: Marcus
authors.identifier: 0000-0002-7071-9067
authors.initials: M
authors.lastname: Bandstein
authors.affiliation: Department of Neuroscience, Functional Pharmacology, Uppsala University, Box 593, 751 24, Uppsala, Sweden.
authors.forename: Sarah
authors.initials: S
authors.lastname: Voisin
authors.affiliation: Department of Neuroscience, Functional Pharmacology, Uppsala University, Box 593, 751 24, Uppsala, Sweden.
authors.forename: Emil K
authors.initials: EK
authors.lastname: Nilsson
authors.affiliation: Interdisciplinary Obesity Center, eSwiss Medical & Surgical Center, St. Gallen, Switzerland.
authors.forename: Bernd
authors.initials: B
authors.lastname: Schultes
authors.affiliation: Interdisciplinary Obesity Center, eSwiss Medical & Surgical Center, St. Gallen, Switzerland.
authors.forename: Barbara
authors.initials: B
authors.lastname: Ernst
authors.affiliation: Interdisciplinary Obesity Center, eSwiss Medical & Surgical Center, St. Gallen, Switzerland.
authors.forename: Martin
authors.initials: M
authors.lastname: Thurnheer
authors.affiliation: Department of Neuroscience, Functional Pharmacology, Uppsala University, Box 593, 751 24, Uppsala, Sweden.
authors.forename: Christian
authors.initials: C
authors.lastname: Benedict
authors.affiliation: Department of Neuroscience, Functional Pharmacology, Uppsala University, Box 593, 751 24, Uppsala, Sweden.
authors.forename: Jessica
authors.initials: J
authors.lastname: Mwinyi
authors.affiliation: Department of Neuroscience, Functional Pharmacology, Uppsala University, Box 593, 751 24, Uppsala, Sweden.
authors.forename: Helgi B
authors.initials: HB
authors.lastname: Schiöth
mesh_terms: D015992:Body Mass Index; D005260:Female; D015390:Gastric Bypass / Q000706:statistics & numerical data*; D055106:Genome-Wide Association Study; D006801:Humans; D008297:Male; D009767:Obesity, Morbid / Q000453:epidemiology / Q000235:genetics / Q000601:surgery; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D012307:Risk Factors; D049629:Waist-Hip Ratio; D015431:Weight Loss / Q000235:genetics*
keywords: Genetic risk score; Obesity; Post-operative weight loss; Random forest model; Roux-en Y gastric bypass surgery
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