Association between Single Nucleotide Polymorphisms and Weight Reduction in Behavioural Interventions-A Pooled Analysis

Christina Holzapfel, Sabine Sag, Johanna Graf-Schindler, Marcus Fischer, Theresa Drabsch, Thomas Illig, Harald Grallert, Lynne Stecher, Christina Strack, Ian D Caterson, Susan A Jebb, Hans Hauner, Andrea Baessler, Christina Holzapfel, Sabine Sag, Johanna Graf-Schindler, Marcus Fischer, Theresa Drabsch, Thomas Illig, Harald Grallert, Lynne Stecher, Christina Strack, Ian D Caterson, Susan A Jebb, Hans Hauner, Andrea Baessler

Abstract

Knowledge of the association between single nucleotide polymorphisms (SNPs) and weight loss is limited. The aim was to analyse whether selected obesity-associated SNPs within the fat mass and obesity-associated (FTO), transmembrane protein 18 (TMEM18), melanocortin-4 receptor (MC4R), SEC16 homolog B (SEC16B), and brain-derived neurotrophic factor (BDNF) gene are associated with anthropometric changes during behavioural intervention for weight loss. genetic and anthropometric data from 576 individuals with overweight and obesity from four lifestyle interventions were obtained. A genetic predisposition score (GPS) was calculated. Our results show that study participants had a mean age of 48.2 ± 12.6 years and a mean baseline body mass index of 33.9 ± 6.4 kg/m2. Mean weight reduction after 12 months was -7.7 ± 10.9 kg. After 12 months of intervention, the MC4R SNPs rs571312 and rs17782313 were significantly associated with a greater decrease in body weight and BMI (p = 0.012, p = 0.011, respectively). The investigated SNPs within the other four genetic loci showed no statistically significant association with changes in anthropometric parameters. The GPS showed no statistically significant association with weight reduction. In conclusion there was no consistent evidence for statistically significant associations of SNPs with anthropometric changes during a behavioural intervention. It seems that other factors play a more significant in weight management than the investigated SNPs.

Keywords: SNP; genetic variant; genotype; weight loss; weight loss program.

Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Genetic predisposition score (GPS) and changes in anthropometric traits. Genetic predisposition score (GPS) and cumulative effects of the risk alleles on changes in body weight, BMI, waist circumference, and fat mass in the combined data. Points represent the mean (± SD) of traits. Bars represent the distribution of GPS. Corresponding linear regression results are shown above each plot after 12 months. n, sample size; beta, regression coefficient; p, p-value; m, meter; cm, centimeter; kg, kilogram; SD, standard deviation. Linear regression adjusted for age, sex, intervention group, and baseline weight.

References

    1. NCD Risk Factor Collaboration Trends in adult body-mass index in 200 countries from 1975 to 2014: A pooled analysis of 1698 population-based measurement studies with 19·2 million participants. Lancet. 2016;387:1377–1396. doi: 10.1016/S0140-6736(16)30054-X.
    1. Blüher M. Obesity: Global epidemiology and pathogenesis. Nat. Rev. Endocrinol. 2019;15:288–298. doi: 10.1038/s41574-019-0176-8.
    1. Semlitsch T., Stigler F., Jeitler K., Horvath K., Siebenhofer A. Management of overweight and obesity in primary care—A systematic overview of international evidence-based guidelines. Obes. Rev. 2019;20:1218–1230. doi: 10.1111/obr.12889.
    1. Hartmann-Boyce J., Boylan A., Jebb S., Fletcher B., Aveyard P. Cognitive and behavioural strategies for self-directed weight loss: Systematic review of qualitative studies. Obes. Rev. 2017;18:335–349. doi: 10.1111/obr.12500.
    1. Matsuo T., Nakata Y., Katayama Y., Iemitsu M., Maeda S., Okura T., Kim M.K., Ohkubo H., Hotta K., Tanaka K. PPARG Genotype Accounts for Part of Individual Variation in Body Weight Reduction in Response to Calorie Restriction. Obesity. 2009;17:1924–1931. doi: 10.1038/oby.2009.199.
    1. Aller E., Mariman E., Bouwman F., van Baak M. Genetic Predictors of ≥5% Weight Loss by Multidisciplinary Advice to Severely Obese Subjects. J. Nutr. Nutr. 2017;10:32–42. doi: 10.1159/000469662.
    1. Dlouhá D., Suchánek P., Lánská V., Hubáček J. Body Mass Index Change in Females After Short-Time Life Style Intervention Is Not Dependent on the FTO Polymorphisms. Physiol. Res. 2011;60:199–202. doi: 10.33549/physiolres.932065.
    1. McCaffery J.M., Papandonatos G.D., Huggins G.S., Peter I., Kahn S.E., Knowler W.C., Hudnall G.E., Lipkin E.W., Kitabchi A.E., Wagenknecht L.E., et al. FTO predicts weight regain in the Look AHEAD clinical trial. Int. J. Obes. 2013;37:1545–1552. doi: 10.1038/ijo.2013.54.
    1. Qi Q., Bray G., Hu F., Sacks F., Qi L. Weight-loss diets modify glucose-dependent insulinotropic polypeptide receptor rs2287019 genotype effects on changes in body weight, fasting glucose, and insulin resistance: The Preventing Overweight Using Novel Dietary Strategies trial. Am. J. Clin. Nutr. 2012;95:506–513. doi: 10.3945/ajcn.111.025270.
    1. Livingstone K.M., Celis-Morales C., Papandonatos G.D., Erar B., Florez J.C., Jablonski K.A., Razquin C., Marti A., Heianza Y., Huang T., et al. FTO genotype and weight loss: Systematic review and meta-analysis of 9563 individual participant data from eight randomised controlled trials. Br. Med. J. 2016;354:i4707. doi: 10.1136/bmj.i4707.
    1. Jebb S.A., Ahern A.L., Olson A.D., Aston L.M., Holzapfel C., Stoll J., Amann-Gassner U., Simpson A.E., Fuller N.R., Pearson S., et al. Primary care referral to a commercial provider for weight loss treatment versus standard care: A randomised controlled trial. Lancet. 2011;378:1485–1492. doi: 10.1016/S0140-6736(11)61344-5.
    1. Bischoff S.C., Damms-Machado A., Betz C., Herpertz S., Legenbauer T., Löw T., Wechsler J.G., Bischoff G., Austel A., Ellrott T. Multicenter evaluation of an interdisciplinary 52-week weight loss program for obesity with regard to body weight, comorbidities and quality of life—A prospective study. Int. J. Obes. 2012;36:614–624. doi: 10.1038/ijo.2011.107.
    1. Speliotes E.K., Willer C.J., Berndt S.I., Monda K.L., Thorleifsson G., Jackson A.U., Allen H.L., Lindgren C.M., Mägi R., Randall J.C., et al. Association analyses of 249,796 individuals reveal 18 new loci associated with body mass index. Nat. Genet. 2010;42:937–948. doi: 10.1038/ng.686.
    1. Walker C.G., Holzapfel C., Loos R.J., Mander A.P., Klopp N., Illig T., Caterson I.D., Hauner H., Jebb S.A. Genetic predisposition to an adverse lipid profile limits the improvement in total cholesterol in response to weight loss. Obesity. 2013;21:2589–2595. doi: 10.1002/oby.20328.
    1. Reich D.E., Cargill M., Bolk S., Ireland J., Sabeti P.C., Richter D.J., Lavery T., Kouyoumjian R., Farhadian S.F., Ward R., et al. Linkage disequilibrium in the human genome. Nature. 2001;411:199–204. doi: 10.1038/35075590.
    1. Li S., Zhao J.H., Luan J.A., Luben R.N., Rodwell S.A., Khaw K.T., Ong K.K., Wareham N.J., Loos R.J. Cumulative effects and predictive value of common obesity-susceptibility variants identified by genome-wide association studies. Am. J. Clin. Nutr. 2010;91:184–190. doi: 10.3945/ajcn.2009.28403.
    1. Pei Y.F., Zhang L., Liu Y., Li J., Shen H., Liu Y.Z., Tian Q., He H., Wu S., Ran S., et al. Meta-analysis of genome-wide association data identifies novel susceptibility loci for obesity. Hum. Mol. Genet. 2014;23:820–830. doi: 10.1093/hmg/ddt464.
    1. Thorleifsson G., Walters G.B., Gudbjartsson D.F., Steinthorsdottir V., Sulem P., Helgadottir A., Styrkarsdottir U., Gretarsdottir S., Thorlacius S., Jonsdottir I., et al. Genome-wide association yields new sequence variants at seven loci that associate with measures of obesity. Nat. Genet. 2009;41:18–24. doi: 10.1038/ng.274.
    1. Locke A.E., Kahali B., Berndt S.I., Justice A.E., Pers T.H., Day F.R., Powell C., Vedantam S., Buchkovich M.L., Yang J., et al. Genetic studies of body mass index yield new insights for obesity biology. Nature. 2015;518:197–206. doi: 10.1038/nature14177.
    1. Willer C.J., Speliotes E.K., Loos R.J., Li S., Lindgren C.M., Heid I.M., Berndt S.I., Elliott A.L., Jackson A.U., Lamina C., et al. Six new loci associated with body mass index highlight a neuronal influence on body weight regulation. Nat. Genet. 2009;41:25–34.
    1. Celis-Morales C., Marsaux C.F., Livingstone K.M., Navas-Carretero S., San-Cristobal R., O’donovan C.B., Forster H., Woolhead C., Fallaize R., Macready A.L., et al. Physical activity attenuates the effect of the FTO genotype on obesity traits in European adults: The Food4Me study. Obesity. 2016;24:962–969. doi: 10.1002/oby.21422.
    1. Frayling T.M., Timpson N.J., Weedon M.N., Zeggini E., Freathy R.M., Lindgren C.M., Perry J.R., Elliott K.S., Lango H., Rayner N.W., et al. A Common Variant in the FTO Gene Is Associated with Body Mass Index and Predisposes to Childhood and Adult Obesity. Science. 2007;316:889–894. doi: 10.1126/science.1141634.
    1. Scuteri A., Sanna S., Chen W.M., Uda M., Albai G., Strait J., Najjar S., Nagaraja R., Orrú M., Usala G., et al. Genome Wide Association Scan shows Genetic Variants in the FTO gene are Associated with Obesity Related Traits. PLoS Genet. 2007;3:e115. doi: 10.1371/journal.pgen.0030115.
    1. Zlatohlavek L., Vrablik M., Motykova E., Ceska R., Vasickova L., Dlouha D., Hubacek J.A. FTO and MC4R gene variants determine BMI changes in children after intensive lifestyle intervention. Clin. Biochem. 2013;46:313–316. doi: 10.1016/j.clinbiochem.2012.11.017.
    1. Pan Q., Delahanty L.M., Jablonski K.A., Knowler W.C., Kahn S.E., Florez J.C., Franks P.W. Diabetes Prevention Program Research Group. Variation at the melanocortin 4 receptor gene and response to weight-loss interventions in the diabetes prevention program. Obesity. 2013;21:E520–E526. doi: 10.1002/oby.20459.
    1. Huang T., Qi Q., Li Y., Hu F.B., Bray G.A., Sacks F.M., Williamson D.A., Qi L. FTO genotype, dietary protein, and change in appetite: The Preventing Overweight Using Novel Dietary Strategies trial. Am. J. Clin. Nutr. 2014;99:1126–1130. doi: 10.3945/ajcn.113.082164.
    1. Woehning A., Schultz J.H., Roeder E., Moeltner A., Isermann B., Nawroth P.P., Wolfrum C., Rudofsky G. The A-allele of the common FTO gene variant rs9939609 complicates weight maintenance in severe obese patients. Int. J. Obes. 2013;37:135–139. doi: 10.1038/ijo.2012.14.
    1. Speakman J. The ‘Fat Mass and Obesity Related’ (FTO) gene: Mechanisms of Impact on Obesity and Energy Balance. Curr. Obes. Rep. 2015;4:73–91. doi: 10.1007/s13679-015-0143-1.
    1. Drabsch T., Gatzemeier J., Pfadenhauer L., Hauner H., Holzapfel C. Associations between Single Nucleotide Polymorphisms and Total Energy, Carbohydrate, and Fat Intakes: A Systematic Review. Adv. Nutr. 2018;9:425–453. doi: 10.1093/advances/nmy024.
    1. Delahanty L.M., Pan Q., Jablonski K.A., Watson K.E., McCaffery J.M., Shuldiner A., Kahn S.E., Knowler W.C., Florez J.C., Franks P.W., et al. Genetic Predictors of Weight Loss and Weight Regain After Intensive Lifestyle Modification, Metformin Treatment, or Standard Care in the Diabetes Prevention Program. Diabetes Care. 2012;35:363–366. doi: 10.2337/dc11-1328.
    1. Zhu J., Loos R.J., Lu L., Zong G., Gan W., Ye X., Sun L., Li H., Lin X. Associations of Genetic Risk Score with Obesity and Related Traits and the Modifying Effect of Physical Activity in a Chinese Han Population. PLoS ONE. 2014;9:e91442. doi: 10.1371/journal.pone.0091442.
    1. Verhoef S., Camps S., Bouwman F., Mariman E., Westerterp K. Genetic predisposition, dietary restraint and disinhibition in relation to short and long-term weight loss. Physiol. Behav. 2014;128:247–251. doi: 10.1016/j.physbeh.2014.02.004.
    1. den Hoed M., Ekelund U., Brage S., Grontved A., Zhao J.H., Sharp S.J., Ong K.K., Wareham N.J., Loos R.J. Genetic Susceptibility to Obesity and Related Traits in Childhood and Adolescence: Influence of Loci Identified by Genome-Wide Association Studies. Diabetes. 2010;59:2980–2988. doi: 10.2337/db10-0370.
    1. Papandonatos G.D., Pan Q., Pajewski N.M., Delahanty L.M., Peter I., Erar B., Ahmad S., Harden M., Chen L., Fontanillas P., et al. Genetic Predisposition to Weight Loss and Regain With Lifestyle Intervention: Analyses From the Diabetes Prevention Program and the Look AHEAD Randomized Controlled Trials. Diabetes. 2015;64:4312–4321. doi: 10.2337/db15-0441.
    1. Gardner C.D., Trepanowski J.F., Del Gobbo L.C., Hauser M.E., Rigdon J., Ioannidis J.P., Desai M., King A.C. Effect of Low-Fat vs Low-Carbohydrate Diet on 12-Month Weight Loss in Overweight Adults and the Association With Genotype Pattern or Insulin Secretion. J. Am. Med Assoc. 2018;319:667–679. doi: 10.1001/jama.2018.0245.

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