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Obesity Surgery

, Volume 29, Issue 8, pp 2554–2561 | Cite as

Genetic Determinants of Weight Loss After Bariatric Surgery

  • Martin AasbrennEmail author
  • Theresia Maria Schnurr
  • Christian Theil Have
  • Mathilde Svendstrup
  • Dorte Lindqvist Hansen
  • Dorte Worm
  • Marie Balslev-Harder
  • Mette Hollensted
  • Niels Grarup
  • Kristoffer Sølvsten Burgdorf
  • Henrik Vestergaard
  • Oluf Pedersen
  • Thorkild I. A. Sørensen
  • Mogens Fenger
  • Sten Madsbad
  • Torben Hansen
Original Contributions

Abstract

Background

The weight loss after bariatric surgery shows considerable individual variation. Twin studies of response to dietary interventions and studies of bariatric surgery patients suggest that genetic differences may play a role. This study aimed to examine the effect of three genetic risk scores on the inter-individual variation in excess body mass index loss (EBMIL) after Roux-en-Y gastric bypass. Furthermore, we searched among known adiposity-related single nucleotide polymorphisms (SNPs) for genetic determinants of the inter-individual variation in EBMIL.

Methods

Patients with morbid obesity underwent Roux-en-Y gastric bypass and were genotyped (n = 577). Two genetic risk scores for weight loss after bariatric surgery and a genetic risk score for body mass index were calculated. Associations between the genetic risk scores and EBMIL were evaluated. Lasso regression was performed on 126 SNPs known to be associated with adiposity.

Results

The average EBMIL was 76.9% (range 21.7–149.2%). EBMIL was 81.1% (SD 20.6) and 73.9% (SD 21.7) in the high and low tertile groups of a genetic risk score for weight loss. Patients with a low genetic risk score for body mass index (in the lowest 5% percentile) had an EBMIL of 68.8% (SD 20.6, p = 0.018). Thirteen adiposity-related SNPs were identified to associate with EBMIL through lasso regression.

Discussion

A genetic risk score was associated with EBMIL after bariatric surgery, but may not yet be applicable to clinical practice. Patients genetically predisposed to low body mass index had lower weight loss after bariatric surgery.

Keywords

Genetic risk scores Weight loss Genetics Gastric bypass Bariatric surgery 

Notes

Compliance with Ethical Standards

Conflict of Interest

The authors declare that they have no conflicts of interest.

Supplementary material

11695_2019_3878_MOESM1_ESM.docx (55 kb)
ESM 1 (DOCX 55 kb)

References

  1. 1.
    Sjostrom L. Review of the key results from the Swedish Obese Subjects (SOS) trial - a prospective controlled intervention study of bariatric surgery. J Intern Med. 2013;273(3):219–34.CrossRefGoogle Scholar
  2. 2.
    Colquitt JL, Pickett K, Loveman E, et al. Surgery for weight loss in adults. Cochrane Database Syst Rev. 2014;8:CD003641.Google Scholar
  3. 3.
    Sjostrom L, Narbro K, Sjostrom CD, et al. Effects of bariatric surgery on mortality in Swedish obese subjects. N Engl J Med. 2007;357(8):741–52.CrossRefGoogle Scholar
  4. 4.
    Hainer V, Stunkard AJ, Kunesova M, et al. Intrapair resemblance in very low calorie diet-induced weight loss in female obese identical twins. Int J Obes Relat Metab Disord. 2000;24(8):1051–7.CrossRefGoogle Scholar
  5. 5.
    Hatoum IJ, Greenawalt DM, Cotsapas C, et al. Heritability of the weight loss response to gastric bypass surgery. J Clin Endocrinol Metab. 2011;96(10):E1630–3.CrossRefGoogle Scholar
  6. 6.
    Bandstein M, Voisin S, Nilsson EK, et al. A genetic risk score is associated with weight loss following Roux-en Y gastric bypass surgery. Obes Surg. 2016;26(9):2183–9.CrossRefGoogle Scholar
  7. 7.
    Rinella ES, Still C, Shao Y, et al. Genome-wide association of single-nucleotide polymorphisms with weight loss outcomes after Roux-en-Y gastric bypass surgery. J Clin Endocrinol Metab. 2013;98(6):E1131–6.CrossRefGoogle Scholar
  8. 8.
    Bandstein M, Mwinyi J, Ernst B, et al. A genetic variant in proximity to the gene LYPLAL1 is associated with lower hunger feelings and increased weight loss following Roux-en-Y gastric bypass surgery. Scand J Gastroenterol. 2016;51(9):1050–5.CrossRefGoogle Scholar
  9. 9.
    Hatoum IJ, Greenawalt DM, Cotsapas C, et al. Weight loss after gastric bypass is associated with a variant at 15q26.1. Am J Hum Genet. 2013;92(5):827–34.CrossRefGoogle Scholar
  10. 10.
    de Toro-Martin J, Guenard F, Tchernof A, et al. Polygenic risk score for predicting weight loss after bariatric surgery. JCI Insight. 2018;3(17).  https://doi.org/10.1172/jci.insight.122011.
  11. 11.
    Locke AE, Kahali B, Berndt SI, et al. Genetic studies of body mass index yield new insights for obesity biology. Nature. 2015;518(7538):197–206.CrossRefGoogle Scholar
  12. 12.
    Shungin D, Winkler TW, Croteau-Chonka DC, et al. New genetic loci link adipose and insulin biology to body fat distribution. Nature. 2015;518(7538):187–96.CrossRefGoogle Scholar
  13. 13.
    Kakela P, Jaaskelainen T, Torpstrom J, et al. Genetic risk score does not predict the outcome of obesity surgery. Obes Surg. 2014;24(1):128–33.CrossRefGoogle Scholar
  14. 14.
    Speliotes EK, Willer CJ, Berndt SI, et al. Association analyses of 249,796 individuals reveal 18 new loci associated with body mass index. Nat Genet. 2010;42(11):937–48.CrossRefGoogle Scholar
  15. 15.
    Heid IM, Jackson AU, Randall JC, et al. Meta-analysis identifies 13 new loci associated with waist-hip ratio and reveals sexual dimorphism in the genetic basis of fat distribution. Nat Genet. 2010;42(11):949–60.CrossRefGoogle Scholar
  16. 16.
    Loos RJ. The genetics of adiposity. Curr Opin Genet Dev. 2018;50:86–95.CrossRefGoogle Scholar
  17. 17.
    Borisenko O, Colpan Z, Dillemans B, et al. Clinical indications, utilization, and funding of bariatric surgery in Europe. Obes Surg. 2015;25(8):1408.CrossRefGoogle Scholar
  18. 18.
    Fenger M, Hansen DL, Worm D, et al. Gastric bypass surgery reveals independency of obesity and diabetes mellitus type 2. BMC Endocr Disord. 2016;16(1):59.CrossRefGoogle Scholar
  19. 19.
    Willer CJ, Li Y, Abecasis GR. METAL: fast and efficient meta-analysis of genomewide association scans. Bioinformatics. 2010;26(17):2190–1.CrossRefGoogle Scholar
  20. 20.
    McCarthy MI. Genomics, type 2 diabetes, and obesity. N Engl J Med. 2010;363(24):2339–50.CrossRefGoogle Scholar
  21. 21.
    Grau K, Cauchi S, Holst C, et al. TCF7L2 rs7903146-macronutrient interaction in obese individuals’ responses to a 10-wk randomized hypoenergetic diet. Am J Clin Nutr. 2010;91(2):472–9.CrossRefGoogle Scholar
  22. 22.
    Svendstrup M. Body fat distribution, metabolic health and weight changes - genetic and epidemiological studies in a prospective design: University of Copenhagen; 2017.Google Scholar
  23. 23.
    Livingstone KM, Celis-Morales C, Papandonatos GD, et al. FTO genotype and weight loss: systematic review and meta-analysis of 9563 individual participant data from eight randomised controlled trials. BMJ. 2016;354:i4707.CrossRefGoogle Scholar
  24. 24.
    Osland E, Yunus RM, Khan S, et al. Weight loss outcomes in laparoscopic vertical sleeve gastrectomy (LVSG) versus laparoscopic Roux-en-Y gastric bypass (LRYGB) procedures: a meta-analysis and systematic review of randomized controlled trials. Surg Laparosc Endosc Percutan Tech. 2017;27(1):8–18.PubMedGoogle Scholar
  25. 25.
    Peterli R, Wolnerhanssen BK, Peters T, et al. Effect of laparoscopic sleeve gastrectomy vs laparoscopic Roux-en-Y gastric bypass on weight loss in patients with morbid obesity: the SM-BOSS randomized clinical trial. JAMA. 2018;319(3):255–65.CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  • Martin Aasbrenn
    • 1
    • 2
    Email author
  • Theresia Maria Schnurr
    • 2
  • Christian Theil Have
    • 2
  • Mathilde Svendstrup
    • 2
    • 3
  • Dorte Lindqvist Hansen
    • 4
  • Dorte Worm
    • 5
  • Marie Balslev-Harder
    • 2
  • Mette Hollensted
    • 2
  • Niels Grarup
    • 2
  • Kristoffer Sølvsten Burgdorf
    • 6
  • Henrik Vestergaard
    • 2
    • 4
  • Oluf Pedersen
    • 2
  • Thorkild I. A. Sørensen
    • 2
    • 7
  • Mogens Fenger
    • 8
  • Sten Madsbad
    • 9
  • Torben Hansen
    • 2
  1. 1.Department of SurgeryInnlandet Hospital TrustGjøvikNorway
  2. 2.Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical SciencesUniversity of CopenhagenCopenhagen NDenmark
  3. 3.Danish Diabetes AcademyOdenseDenmark
  4. 4.Steno Diabetes Center CopenhagenGentofteDenmark
  5. 5.Department of MedicineAmager HospitalKøbenhavnDenmark
  6. 6.Department of Clinical ImmunologyCopenhagen University HospitalCopenhagenDenmark
  7. 7.Department of Public Health, Faculty of Health and Medical SciencesUniversity of CopenhagenCopenhagenDenmark
  8. 8.Department of Clinical BiochemistryHvidovre University HospitalCopenhagenDenmark
  9. 9.Department of EndocrinologyHvidovre University HospitalCopenhagenDenmark

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