Skip to main content
Top
Published in: Obesity Surgery 8/2019

01-08-2019 | Obesity | Original Contributions

Genetic Determinants of Weight Loss After Bariatric Surgery

Authors: Martin Aasbrenn, 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

Published in: Obesity Surgery | Issue 8/2019

Login to get access

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.
Appendix
Available only for authorised users
Literature
1.
go back to reference 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.CrossRef 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.CrossRef
2.
go back to reference Colquitt JL, Pickett K, Loveman E, et al. Surgery for weight loss in adults. Cochrane Database Syst Rev. 2014;8:CD003641. Colquitt JL, Pickett K, Loveman E, et al. Surgery for weight loss in adults. Cochrane Database Syst Rev. 2014;8:CD003641.
3.
go back to reference 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.CrossRef 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.CrossRef
4.
go back to reference 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.CrossRef 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.CrossRef
5.
go back to reference 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.CrossRef 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.CrossRef
6.
go back to reference 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.CrossRef 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.CrossRef
7.
go back to reference 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.CrossRef 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.CrossRef
8.
go back to reference 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.CrossRef 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.CrossRef
9.
go back to reference 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.CrossRef 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.CrossRef
11.
go back to reference 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.CrossRef 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.CrossRef
12.
go back to reference 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.CrossRef 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.CrossRef
13.
go back to reference 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.CrossRef 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.CrossRef
14.
go back to reference 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.CrossRef 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.CrossRef
15.
go back to reference 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.CrossRef 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.CrossRef
16.
17.
go back to reference Borisenko O, Colpan Z, Dillemans B, et al. Clinical indications, utilization, and funding of bariatric surgery in Europe. Obes Surg. 2015;25(8):1408.CrossRef Borisenko O, Colpan Z, Dillemans B, et al. Clinical indications, utilization, and funding of bariatric surgery in Europe. Obes Surg. 2015;25(8):1408.CrossRef
18.
go back to reference 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.CrossRef 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.CrossRef
19.
go back to reference Willer CJ, Li Y, Abecasis GR. METAL: fast and efficient meta-analysis of genomewide association scans. Bioinformatics. 2010;26(17):2190–1.CrossRef Willer CJ, Li Y, Abecasis GR. METAL: fast and efficient meta-analysis of genomewide association scans. Bioinformatics. 2010;26(17):2190–1.CrossRef
20.
go back to reference McCarthy MI. Genomics, type 2 diabetes, and obesity. N Engl J Med. 2010;363(24):2339–50.CrossRef McCarthy MI. Genomics, type 2 diabetes, and obesity. N Engl J Med. 2010;363(24):2339–50.CrossRef
21.
go back to reference 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.CrossRef 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.CrossRef
22.
go back to reference Svendstrup M. Body fat distribution, metabolic health and weight changes - genetic and epidemiological studies in a prospective design: University of Copenhagen; 2017. Svendstrup M. Body fat distribution, metabolic health and weight changes - genetic and epidemiological studies in a prospective design: University of Copenhagen; 2017.
23.
go back to reference 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.CrossRef 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.CrossRef
24.
go back to reference 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.PubMed 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.PubMed
25.
go back to reference 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.CrossRef 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.CrossRef
Metadata
Title
Genetic Determinants of Weight Loss After Bariatric Surgery
Authors
Martin Aasbrenn
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
Publication date
01-08-2019
Publisher
Springer US
Published in
Obesity Surgery / Issue 8/2019
Print ISSN: 0960-8923
Electronic ISSN: 1708-0428
DOI
https://doi.org/10.1007/s11695-019-03878-5

Other articles of this Issue 8/2019

Obesity Surgery 8/2019 Go to the issue