Interplay between diet and genetic susceptibility in obesity and related traits
Tiange Wang, Min Xu, Yufang Bi, Guang Ning()
State Key Laboratory of Medical Genomics, Key Laboratory for Endocrine and Metabolic Diseases of the Ministry of Health, National Clinical Research Center for Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Department of Endocrine and Metabolic Diseases, Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China
The incidence of obesity has been rapidly increasing, and this condition has become a major public health threat. A substantial shift in environmental factors and lifestyle, such as unhealthy diet, is among the major driving forces of the global obesity pandemic. Longitudinal studies and randomized intervention trials have shown that genetic susceptibility to obesity may interact with dietary factors in relation to the body mass index and risk of obesity. This review summarized data from recent longitudinal studies and intervention studies on variations and diets and discussed the challenges and future prospects related to this area and public health implications.
. [J]. Frontiers of Medicine, 2018, 12(6): 601-607.
Tiange Wang, Min Xu, Yufang Bi, Guang Ning. Interplay between diet and genetic susceptibility in obesity and related traits. Front. Med., 2018, 12(6): 601-607.
A genetic risk score based on 32 BMI-associated loci
High consumption of sugar-sweetened beverages may amplify the genetic association with higher BMI and obesity risk
Brunkwall et al. 2016 [11]
Sugar-sweetened beverages
A genetic risk score based on 30 BMI-associated loci
The relation of sugar-sweetened beverages intake and BMI is strong in people genetically predisposed to obesity
Wang et al. 2017 [12]
Coffee
A genetic risk score based on 77 BMI-associated loci
High habitual coffee consumption may attenuate the genetic association with high BMI and obesity risk
Corella et al. 2009 [13]
Saturated fat
APOA2-265T>C polymorphism
Individuals with the APOA2 CC genotype show increased susceptibility to increased BMI and obesity when they consume a high-saturated fat diet
Qi et al. 2014 [14]
Fried food
A genetic risk score based on 32 BMI-associated loci
Higher frequency of fried food consumption may amplify the genetic association with high BMI and obesity risk
Nettleton et al. 2015 [15]
A diet score based on whole grains, fish, fruits, vegetables, nuts/seeds (favorable) and red/processed meats, sweets, sugar-sweetened beverages, and fried potatoes (unfavorable)
A genetic risk score based on 18 WHR-associated loci
The associations between genetic predisposition and obesity traits were strong with a healthy diet
Wang et al. 2018 [16]
Two diet score: Alternate Healthy Eating Index 2010 and Dietary Approach to Stop Hypertension
A genetic risk score based on 77 BMI-associated loci
The association between a healthy diet and weight loss was strong in participants with a great genetic predisposition to obesity
Tab.1
Studies
Study design
Genetic factors
Major findings
Qi et al. 2011 [19]
N = 738; 2-y diet intervention
Diabetes-associated IRS1 rs2943641
IRS1 genetic variants modify effects of dietary carbohydrate on weight loss and insulin resistance
Erez et al. 2011 [20]
N = 322; 2-y diet intervention
Obesity-related LEP variants
LEP genotype is related to weight regain from 7–24 m
Mattei et al. 2012 [21]
N = 591; 2-y diet intervention
Diabetes-associated TCF7L2 variant rs7903146
Dietary fat intake interacts with TCF7L2 genotype in relation to changes in BMI, total fat mass, and trunk fat mass
Zhang et al. 2012 [22]
N = 742; 2-y diet intervention
Obesity-related FTO variant rs1558902
High-protein diet interacts with FTO genotype in relation to weight loss and improvement of body composition and fat distribution
Heni et al. 2012 [23]
N = 304; 9-m diet intervention
Diabetes-associated TCF7L2 variant rs7903146
CC genotype is associated with great weight loss in participants with high fiber intake but not those with low fiber intake
Zhang et al. 2012 [24]
N = 734; 2-y diet intervention
Lipid metabolism-related APOA5 variant rs964184
Dietary fat interacts with APOA5 genotype in relation to 2-y changes in lipid profile
Zhang et al. 2012 [25]
N = 723; 2-y diet intervention
Hypertension-associated NPY variant rs16147
NPY genotype modifies effects of dietary fat on 2-y changes of blood pressure
Larsen et al. 2012 [26]
N = 742; 6-m diet intervention on weight loss maintenance
768 tag SNPs for nutrient-sensitive genes
Multiple interactions with GI or dietary protein on waist and fat mass regain
Qi et al. 2012 [27]
N = 737; 2-y diet intervention
Diabetes-related GIPR variant rs2287019
Dietary carbohydrate modified GIPR genotype effects on changes in bodyweight, fasting glucose, and insulin resistance
Xu, et al. 2013 [28]
N = 734; 2-y diet intervention
BCAA-associated PPM1K SNP rs1440581
Dietary fat significantly modifies genetic effects on changes in weight and fasting insulin
Brahe et al. 2013 [29]
N = 841 (baseline); 6-m diet intervention on weight loss maintenance
240 tag SNPs for candidate genes
LPIN1 SNP rs4315495 genotype interacts with dietary protein on change of TG concentration
McCaffery et al. 2013 [30]
N = 3899; 4-y lifestyle intervention in diabetic patients
Obesity-related variants
Variations in the FTO and BDNF loci are related to weight regain after weight loss
Pan et al. 2013 [31]
N = 3819; 2-y intervention; lifestyle modification and metformin
Obesity-related MC4R variants
rs17066866 is associated with less short-term (baseline to 6 m) and less long-term (baseline to 2 y) weight loss in the lifestyle intervention group but not in placebo group
Kostis et al. 2013 [32]
N = 722; 4-m intervention; diet and medication
21 SNPs related to hypertension, diabetes, or obesity
Multiple genotypes are related to change in blood pressures in response to diet intervention
Qi et al. 2013 [33]
POUNDS Lost: N = 738; 2-y diet intervention
Diabetes-associated IRS1 rs2943641 and rs1522813
High-fat weight-loss diets may be more effective in the management of the metabolic syndrome compared with low-fat diets among individuals with the A-allele of the rs1522813 variant near IRS1
Mirzaei et al. 2014 [34]
N = 721; 2-y diet intervention
Circadian-related genes CRY2 and MTNR1B
Variants in CRY2 and MTNR1B may affect long-term changes in energy expenditure, and dietary fat intake may modify the genetic effects
Huang et al. 2015 [35]
N = 730; 2-y diet intervention
Iron homeostasis-related PCSK7 variant
PCSK7 genotypes may interact with dietary carbohydrate intake on changes in insulin sensitivity
Qi et al. 2015 [36]
POUNDS Lost: N = 732; 2-y diet intervention; DIRECT: N = 171; 2-y diet intervention
Cholesterol-related CETP variant
Individuals with the CETP rs3764261 CC genotype may derive great effects on raising HDL cholesterol and lowering triglycerides by choosing a low-carbohydrate/high-fat weight-loss diet instead of a low-fat diet
Zheng et al. 2015 [37]
N = 743; 2-y diet intervention
Obesity-associated FTO variant
Carriers of the risk alleles of rs1558902 benefit differently in improving insulin sensitivity by consuming high-fat weight-loss diets rather than low-fat diets
Lin et al. 2015 [38]
N = 723; 2-y diet intervention
Obesity-associated NPY variant
NPY rs16147 genotypes affect the change in abdominal adiposity in response to dietary interventions
Qi et al. 2015 [39]
N = 721; 2-y diet intervention
Three vitamin D metabolism-related variants
Individuals carrying the T allele of DHCR7 rs12785878 may benefit more in improvement of insulin resistance than non-carriers by consuming high-protein weight-loss diets
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4
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9
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10
Qi Q, Chu AY, Kang JH, Jensen MK, Curhan GC, Pasquale LR, Ridker PM, Hunter DJ, Willett WC, Rimm EB, Chasman DI, Hu FB, Qi L. Sugar-sweetened beverages and genetic risk of obesity. N Engl J Med 2012; 367(15): 1387–1396 https://doi.org/10.1056/NEJMoa1203039
pmid: 22998338
11
Brunkwall L, Chen Y, Hindy G, Rukh G, Ericson U, Barroso I, Johansson I, Franks PW, Orho-Melander M, Renström F. Sugar-sweetened beverage consumption and genetic predisposition to obesity in 2 Swedish cohorts. Am J Clin Nutr 2016; 104(3): 809–815 https://doi.org/10.3945/ajcn.115.126052
pmid: 27465381
12
Wang T, Huang T, Kang JH, Zheng Y, Jensen MK, Wiggs JL, Pasquale LR, Fuchs CS, Campos H, Rimm EB, Willett WC, Hu FB, Qi L. Habitual coffee consumption and genetic predisposition to obesity: gene–diet interaction analyses in three US prospective studies. BMC Med 2017; 15(1): 97 https://doi.org/10.1186/s12916-017-0862-0
pmid: 28486942
13
Corella D, Peloso G, Arnett DK, Demissie S, Cupples LA, Tucker K, Lai CQ, Parnell LD, Coltell O, Lee YC, Ordovas JM. APOA2, dietary fat, and body mass index: replication of a gene–diet interaction in 3 independent populations. Arch Intern Med 2009; 169(20): 1897–1906 https://doi.org/10.1001/archinternmed.2009.343
pmid: 19901143
14
Qi Q, Chu AY, Kang JH, Huang J, Rose LM, Jensen MK, Liang L, Curhan GC, Pasquale LR, Wiggs JL, De Vivo I, Chan AT, Choi HK, Tamimi RM, Ridker PM, Hunter DJ, Willett WC, Rimm EB, Chasman DI, Hu FB, Qi L. Fried food consumption, genetic risk, and body mass index: gene–diet interaction analysis in three US cohort studies. BMJ 2014; 348(mar19 1): g1610 https://doi.org/10.1136/bmj.g1610
pmid: 24646652
15
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pmid: 25994509
16
Wang T, Heianza Y, Sun D, Huang T, Ma W, Rimm EB, Manson JE, Hu FB, Willett WC, Qi L. Improving adherence to healthy dietary patterns, genetic risk, and long term weight gain: gene–diet interaction analysis in two prospective cohort studies. BMJ 2018; 360: j5644 https://doi.org/10.1136/bmj.j5644
pmid: 29321156
17
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pmid: 28436986
18
Stojkovic IA, Ericson U, Rukh G, Riddestråle M, Romeo S, Orho-Melander M. The PNPLA3 Ile148Met interacts with overweight and dietary intakes on fasting triglyceride levels. Genes Nutr 2014; 9(2): 388 https://doi.org/10.1007/s12263-014-0388-4
pmid: 24563329
19
Qi Q, Bray GA, Smith SR, Hu FB, Sacks FM, Qi L. Insulin receptor substrate 1 gene variation modifies insulin resistance response to weight-loss diets in a 2-year randomized trial: the Preventing Overweight Using Novel Dietary Strategies (POUNDS LOST) trial. Circulation 2011; 124(5): 563–571 https://doi.org/10.1161/CIRCULATIONAHA.111.025767
pmid: 21747052
20
Erez G, Tirosh A, Rudich A, Meiner V, Schwarzfuchs D, Sharon N, Shpitzen S, Blüher M, Stumvoll M, Thiery J, Fiedler GM, Friedlander Y, Leiterstdorf E, Shai I. Phenotypic and genetic variation in leptin as determinants of weight regain. Int J Obes 2011; 35(6): 785–792 https://doi.org/10.1038/ijo.2010.217
pmid: 21042325
21
Mattei J, Qi Q, Hu FB, Sacks FM, Qi L. TCF7L2 genetic variants modulate the effect of dietary fat intake on changes in body composition during a weight-loss intervention. Am J Clin Nutr 2012; 96(5): 1129–1136 https://doi.org/10.3945/ajcn.112.038125
pmid: 23034957
22
Zhang X, Qi Q, Zhang C, Smith SR, Hu FB, Sacks FM, Bray GA, Qi L. FTO genotype and 2-year change in body composition and fat distribution in response to weight-loss diets: the POUNDS LOST Trial. Diabetes 2012; 61(11): 3005–3011 https://doi.org/10.2337/db11-1799
pmid: 22891219
23
Heni M, Herzberg-Schäfer S, Machicao F, Häring HU, Fritsche A. Dietary fiber intake modulates the association between variants in TCF7L2 and weight loss during a lifestyle intervention. Diabetes Care 2012; 35(3): e24 https://doi.org/10.2337/dc11-2012
pmid: 22355027
24
Zhang X, Qi Q, Bray GA, Hu FB, Sacks FM, Qi L. APOA5 genotype modulates 2-y changes in lipid profile in response to weight-loss diet intervention: the Pounds Lost Trial. Am J Clin Nutr 2012; 96(4): 917–922 https://doi.org/10.3945/ajcn.112.040907
pmid: 22914552
25
Zhang X, Qi Q, Liang J, Hu FB, Sacks FM, Qi L. Neuropeptide Y promoter polymorphism modifies effects of a weight-loss diet on 2-year changes of blood pressure: the preventing overweight using novel dietary strategies trial. Hypertension 2012; 60(5): 1169–1175 https://doi.org/10.1161/HYPERTENSIONAHA.112.197855
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26
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pmid: 22492381
27
Qi Q, Bray GA, Hu FB, Sacks FM, 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(2): 506–513 https://doi.org/10.3945/ajcn.111.025270
pmid: 22237064
28
Xu M, Qi Q, Liang J, Bray GA, Hu FB, Sacks FM, Qi L. Genetic determinant for amino acid metabolites and changes in body weight and insulin resistance in response to weight-loss diets: the Preventing Overweight Using Novel Dietary Strategies (POUNDS LOST) trial. Circulation 2013; 127(12): 1283–1289 https://doi.org/10.1161/CIRCULATIONAHA.112.000586
pmid: 23446828
29
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pmid: 23360819
30
McCaffery JM, Papandonatos GD, Huggins GS, Peter I, Kahn SE, Knowler WC, Hudnall GE, Lipkin EW, Kitabchi AE, Wagenknecht LE, Wing RR. FTO predicts weight regain in the Look AHEAD clinical trial. Int J Obes 2013; 37(12): 1545–1552 https://doi.org/10.1038/ijo.2013.54
pmid: 23628854
31
Pan Q, Delahanty LM, Jablonski KA, Knowler WC, Kahn SE, Florez JC, Franks PW; Diabetes Prevention Program Research Group. Variation at the melanocortin 4 receptor gene and response to weight-loss interventions in the diabetes prevention program. Obesity (Silver Spring) 2013; 21(9): E520–E526
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32
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33
Qi Q, Xu M, Wu H, Liang L, Champagne CM, Bray GA, Sacks FM, Qi L. IRS1 genotype modulates metabolic syndrome reversion in response to 2-year weight-loss diet intervention: the POUNDS LOST trial. Diabetes Care 2013; 36(11): 3442–3447 https://doi.org/10.2337/dc13-0018
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34
Mirzaei K, Xu M, Qi Q, de Jonge L, Bray GA, Sacks F, Qi L. Variants in glucose- and circadian rhythm-related genes affect the response of energy expenditure to weight-loss diets: the POUNDS LOST Trial. Am J Clin Nutr 2014; 99(2): 392–399 https://doi.org/10.3945/ajcn.113.072066
pmid: 24335056
35
Huang T, Huang J, Qi Q, Li Y, Bray GA, Rood J, Sacks FM, Qi L. PCSK7 genotype modifies effect of a weight-loss diet on 2-year changes of insulin resistance: the POUNDS LOST trial. Diabetes Care 2015; 38(3): 439–444 https://doi.org/10.2337/dc14-0473
pmid: 25504030
36
Qi Q, Durst R, Schwarzfuchs D, Leitersdorf E, Shpitzen S, Li Y, Wu H, Champagne CM, Hu FB, Stampfer MJ, Bray GA, Sacks FM, Shai I, Qi L. CETP genotype and changes in lipid levels in response to weight-loss diet intervention in the POUNDS LOST and DIRECT randomized trials. J Lipid Res 2015; 56(3): 713–721 https://doi.org/10.1194/jlr.P055715
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37
Zheng Y, Huang T, Zhang X, Rood J, Bray GA, Sacks FM, Qi L. Dietary fat modifies the effects of FTO genotype on changes in insulin sensitivity. J Nutr 2015; 145(5): 977–982 https://doi.org/10.3945/jn.115.210005
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38
Lin X, Qi Q, Zheng Y, Huang T, Lathrop M, Zelenika D, Bray GA, Sacks FM, Liang L, Qi L. Neuropeptide Y genotype, central obesity, and abdominal fat distribution: the POUNDS LOST trial. Am J Clin Nutr 2015; 102(2): 514–519 https://doi.org/10.3945/ajcn.115.107276
pmid: 26156739
39
Qi Q, Zheng Y, Huang T, Rood J, Bray GA, Sacks FM, Qi L. Vitamin D metabolism-related genetic variants, dietary protein intake and improvement of insulin resistance in a 2 year weight-loss trial: POUNDS Lost. Diabetologia 2015; 58(12): 2791–2799 https://doi.org/10.1007/s00125-015-3750-1
pmid: 26416604
40
Sacks FM, Bray GA, Carey VJ, Smith SR, Ryan DH, Anton SD, McManus K, Champagne CM, Bishop LM, Laranjo N, Leboff MS, Rood JC, de Jonge L, Greenway FL, Loria CM, Obarzanek E, Williamson DA. Comparison of weight-loss diets with different compositions of fat, protein, and carbohydrates. N Engl J Med 2009; 360(9): 859–873 https://doi.org/10.1056/NEJMoa0804748
pmid: 19246357