Low-frequency Coding Variants Associated With Body Mass Index Affect the Success of Bariatric Surgery Academic Article uri icon

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  • Abstract Context A recent study identified 14 low-frequency coding variants associated with body mass index (BMI) in 718 734 individuals predominantly of European ancestry. Objective We investigated the association of 2 genetic scores (GS) with i) the risk of severe/morbid obesity, ii) BMI variation before weight-loss intervention, iii) BMI change in response to an 18-month lifestyle/behavioral intervention program, and iv) BMI change up to 24 months after bariatric surgery. Methods The 14 low-frequency coding variants were genotyped or sequenced in 342 French adults with severe/morbid obesity and 574 French adult controls from the general population. We built risk and protective GS based on 6 BMI-increasing and 5 BMI-decreasing low-frequency coding variants that were polymorphic in our study. Results While the risk GS was not associated with severe/morbid obesity status, BMI-decreasing low-frequency coding variants were significantly less frequent in patients with severe/morbid obesity than in French adults from the general population. Neither the risk nor the protective GS was associated with BMI before intervention in patients with severe/morbid obesity, nor did they affect BMI change in response to a lifestyle/behavioral modification program. The protective GS was associated with a greater BMI decrease following bariatric surgery. The risk and protective GS were associated with a higher and lower risk of BMI regain after bariatric surgery. Conclusion Our data indicate that in populations of European descent, low-frequency coding variants associated with BMI in the general population also affect the outcomes of bariatric surgery in patients with severe/morbid obesity.


  • Antoine, Darlène
  • Guéant-Rodriguez, Rosa-Maria
  • Chèvre, Jean-Claude
  • Hergalant, Sébastien
  • Sharma, Tanmay
  • Li, Zhen
  • Rouyer, Pierre
  • Chery, Céline
  • Halvick, Sarah
  • Bui, Catherine
  • Oussalah, Abderrahim
  • Ziegler, Olivier
  • Quilliot, Didier
  • Brunaud, Laurent
  • Guéant, Jean-Louis
  • Meyre, David Jean-Claude

publication date

  • February 17, 2022