title: Heritability of the weight loss response to gastric bypass surgery.
abstract: BACKGROUND
  The use of Roux-en-Y gastric bypass (RYGB) surgery to treat severe obesity has grown dramatically. RYGB is highly effective, but the response in individual patients varies widely, and clinical predictors have been able to explain only a fraction of this variation.
  
  
  OBJECTIVE
  Our objective was to determine whether there is a significant genetic contribution to weight loss after RYGB.
  
  
  METHODS
  We genotyped 848 patients undergoing RYGB. Using identity-by-descent methods, we identified 13 pairs of first-degree relatives. We identified an additional 10 pairs of individuals who were living together but are not genetically related and randomly paired the remaining 794 individuals. We then compared weight loss within and across pairs.
  
  
  RESULTS
  First-degree relative pairs had a similar response to surgery, with a 9% mean difference in excess weight loss between members of each pair. This similarity was not seen with cohabitating individuals (26% mean difference; P = 0.005 vs. first-degree pairs) or unrelated individuals (25% mean difference; P = 0.001). Cohabitating individuals had within-pair differences in weight loss no more similar than randomly paired individuals (P = 0.60). The pair relationship explained a significant portion of the variation in weight loss in first-degree relatives [intraclass correlation coefficient (ICC) = 70.4%; P = 0.02] but not in random subjects (ICC = 0.9%; P = 0.48) or genetically unrelated cohabitating individuals (ICC = 14.3%; P = 0.67).
  
  
  CONCLUSIONS
  Genetic factors strongly influence the effect of RYGB on body weight. Identification of the specific genes that mediate this effect will advance our understanding of the biological mechanisms of weight loss after RYGB and should help identify patients who will benefit the most from this intervention.
authors.affiliation: Gastrointestinal Metabolism Laboratory and Gastrointestinal Unit, Massachusetts General Hospital, Boston, Massachusetts 02114, USA.
authors.forename: Ida J
authors.initials: IJ
authors.lastname: Hatoum
authors.forename: Danielle M
authors.initials: DM
authors.lastname: Greenawalt
authors.forename: Chris
authors.initials: C
authors.lastname: Cotsapas
authors.forename: Marc L
authors.initials: ML
authors.lastname: Reitman
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Daly
authors.forename: Lee M
authors.initials: LM
authors.lastname: Kaplan
mesh_terms: D000328:Adult; D015331:Cohort Studies; D023381:Endpoint Determination; D005190:Family; D005260:Female; D015390:Gastric Bypass / Q000379:methods*; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000235:genetics* / Q000601:surgery*; D013270:Stomach / Q000601:surgery*; D016896:Treatment Outcome; D015431:Weight Loss / Q000235:genetics*