A genetic risk tool for obesity predisposition assessment and personalized nutrition implementation based on macronutrient intake

There is little evidence about genetic risk score (GRS)–diet interactions in order to provide personalized nutrition based on the genotype. The aim of the study was to assess the value of a GRS on obesity prediction and to further evaluate the interactions between the GRS and dietary intake on obesity. A total of 711 seekers of a Nutrigenetic Service were examined for anthropometric and body composition measurements and also for dietary habits and physical activity. Oral epithelial cells were collected for the identification of 16 SNPs (related with obesity or lipid metabolism) using DNA zip-coded beads. Genotypes were coded as 0, 1 or 2 according to the number of risk alleles, and the GRS was calculated by adding risk alleles with such a criterion. After being adjusted for gender, age, physical activity and energy intake, the GRS demonstrated that individuals carrying >7 risk alleles had in average 0.93 kg/m2 of BMI, 1.69 % of body fat mass, 1.94 cm of waist circumference and 0.01 waist-to-height ratio more than the individuals with ≤7 risk alleles. Significant interactions for GRS and the consumption of energy, total protein, animal protein, vegetable protein, total fat, saturated fatty acids, polyunsaturated fatty acids, total carbohydrates, complex carbohydrates and fiber intake on adiposity traits were found after adjusted for confounders variables. The GRS confirmed that the high genetic risk group showed greater values of adiposity than the low risk group and demonstrated that macronutrient intake modifies the GRS association with adiposity traits.

[1]  D. Allison,et al.  Obesity polymorphisms identified in genome-wide association studies interact with n-3 polyunsaturated fatty acid intake and modify the genetic association with adiposity phenotypes in Yup’ik people , 2013, Genes & Nutrition.

[2]  A. Martí,et al.  Pro12Ala variant of the PPARG2 gene increases body mass index: An updated meta‐analysis encompassing 49,092 subjects , 2013, Obesity.

[3]  S. Gortmaker,et al.  Health and economic burden of the projected obesity trends in the USA and the UK , 2011, The Lancet.

[4]  Erik Ingelsson,et al.  Genome-wide association studies of obesity and metabolic syndrome , 2014, Molecular and Cellular Endocrinology.

[5]  Mario Cleves,et al.  Receiver Operating Characteristic (ROC) anaylsis , 2000 .

[6]  J. Tuomilehto,et al.  Association of the fat mass and obesity-associated (FTO) gene variant (rs9939609) with dietary intake in the Finnish Diabetes Prevention Study. , 2012, The British journal of nutrition.

[7]  L. Pérusse,et al.  The PPAR‐gamma P12A polymorphism modulates the relationship between dietary fat intake and components of the metabolic syndrome: results from the Québec Family Study , 2003, Clinical genetics.

[8]  Sociedad Española para el Estudio de la Obesidad.  Consenso SEEDO'2000 para la evaluación del sobrepeso y la obesidad y el establecimiento de criterios de intervención terapéutica , 2000 .

[9]  M. Arranz,et al.  Apolipoprotein-E gene variants associated with cardiovascular risk factors in antipsychotic recipients , 2009, European Psychiatry.

[10]  Audrey Y. Chu,et al.  Gene × Physical Activity Interactions in Obesity: Combined Analysis of 111,421 Individuals of European Ancestry , 2013, PLoS genetics.

[11]  Elisavet H. Fotiadou,et al.  Mechanisms of obesity and related pathologies: Role of apolipoprotein E in the development of obesity , 2009, The FEBS journal.

[12]  R. Collins,et al.  Newly identified loci that influence lipid concentrations and risk of coronary artery disease , 2008, Nature Genetics.

[13]  M. Orho-Melander,et al.  Fat and carbohydrate intake modify the association between genetic variation in the FTO genotype and obesity. , 2009, The American journal of clinical nutrition.

[14]  Jing Hua Zhao,et al.  Physical Activity Attenuates the Genetic Predisposition to Obesity in 20,000 Men and Women from EPIC-Norfolk Prospective Population Study , 2010, PLoS medicine.

[15]  Subhajyoti De,et al.  Common variants near MC4R are associated with fat mass, weight and risk of obesity , 2008, Nature Genetics.

[16]  Paul W. Franks,et al.  Replication and extension of genome-wide association study results for obesity in 4923 adults from northern Sweden , 2009, Human molecular genetics.

[17]  Anne E Sumner,et al.  A Better Index of Body Adiposity , 2011, Obesity.

[18]  C. Bouchard,et al.  Advances in exercise, fitness, and performance genomics in 2011. , 2012, Medicine and science in sports and exercise.

[19]  Christian Gieger,et al.  Six new loci associated with body mass index highlight a neuronal influence on body weight regulation , 2009, Nature Genetics.

[20]  Ce. Metz,et al.  Receiver operating characteristic (ROC) analysis in medical imaging , 1997 .

[21]  F. Hu,et al.  Obesity Genotype Score and Cardiovascular Risk in Women With Type 2 Diabetes Mellitus , 2010, Arteriosclerosis, thrombosis, and vascular biology.

[22]  F. Takeuchi,et al.  Association of genetic variants for susceptibility to obesity with type 2 diabetes in Japanese individuals , 2011, Diabetologia.

[23]  Martin N. Rossor,et al.  GENETICS OF ALZHEIMERS-DISEASE , 1990 .

[24]  J. Ordovás,et al.  PPARγ Pro12Ala interacts with fat intake for obesity and weight loss in a behavioural treatment based on the Mediterranean diet. , 2011, Molecular nutrition & food research.

[25]  C. Drevon,et al.  NOS3 gene polymorphisms are associated with risk markers of cardiovascular disease, and interact with omega-3 polyunsaturated fatty acids. , 2010, Atherosclerosis.

[26]  M. Jarvelin,et al.  A Common Variant in the FTO Gene Is Associated with Body Mass Index and Predisposes to Childhood and Adult Obesity , 2007, Science.

[27]  P. Froguel,et al.  Meal Frequencies Modify the Effect of Common Genetic Variants on Body Mass Index in Adolescents of the Northern Finland Birth Cohort 1986 , 2013, PloS one.

[28]  F. Milagro,et al.  Future challenges and present ethical considerations in the use of personalized nutrition based on genetic advice. , 2013, Journal of the Academy of Nutrition and Dietetics.

[29]  Frank B Hu,et al.  Genetics of type 2 diabetes in European populations , 2012, Journal of diabetes.

[30]  S. Hercberg,et al.  High dietary saturated fat intake accentuates obesity risk associated with the fat mass and obesity-associated gene in adults. , 2012, The Journal of nutrition.

[31]  R. Luben,et al.  Cumulative effects and predictive value of common obesity-susceptibility variants identified by genome-wide association studies. , 2010, The American journal of clinical nutrition.

[32]  O. Melander,et al.  Genetic susceptibility to obesity and diet intakes: association and interaction analyses in the Malmö Diet and Cancer Study , 2013, Genes & Nutrition.

[33]  S. Dunbar.  Applications of Luminex® xMAP™ technology for rapid, high-throughput multiplexed nucleic acid detection , 2005, Clinica Chimica Acta.

[34]  Shah Ebrahim,et al.  The methylenetetrahydrofolate reductase C677T genotype and the risk of obesity in three large population-based cohorts , 2008, European journal of endocrinology.

[35]  E. Rimm,et al.  Sugar-Sweetened Beverages and Genetic Risk of Obesity , 2013 .

[36]  Generating Genetic Risk Scores from Intermediate Phenotypes for Use in Association Studies of Clinically Significant Endpoints , 2005 .

[37]  Audrey Y. Chu,et al.  Fried food consumption, genetic risk, and body mass index: gene-diet interaction analysis in three US cohort studies , 2014, BMJ : British Medical Journal.

[38]  Markus Perola,et al.  Genome-wide association study identifies multiple loci influencing human serum metabolite levels , 2012, Nature Genetics.

[39]  Mark T. W. Ebbert,et al.  Genetics of Alzheimer's Disease , 2013, BioMed research international.

[40]  N. Cox,et al.  Obesity-associated variants within FTO form long-range functional connections with IRX3 , 2014, Nature.

[41]  Lifestyle factors modify obesity risk linked to PPARG2 and FTO variants in an elderly population: a cross-sectional analysis in the SUN Project , 2012, Genes & Nutrition.

[42]  R. Cooper,et al.  Impact of obesity-related genes in Spanish population , 2013, BMC Genetics.

[43]  D. Dorfman,et al.  Maximum-likelihood estimation of parameters of signal-detection theory and determination of confidence intervals—Rating-method data , 1969 .

[44]  Jianxin Shi,et al.  Genetic risk sum score comprised of common polygenic variation is associated with body mass index , 2011, Human Genetics.

[45]  Youfa Wang,et al.  Variation in the heritability of body mass index based on diverse twin studies: a systematic review , 2013, Obesity reviews : an official journal of the International Association for the Study of Obesity.

[46]  J. Hirschhorn,et al.  An age-dependent diet-modified effect of the PPARγ Pro12Ala polymorphism in children. , 2011, Metabolism: clinical and experimental.

[47]  A. Astrup,et al.  Obesity and the metabolic syndrome: role of different dietary macronutrient distribution patterns and specific nutritional components on weight loss and maintenance. , 2010, Nutrition reviews.

[48]  G. Cascio,et al.  Dietary fatty acids in metabolic syndrome, diabetes and cardiovascular diseases. , 2012, Current diabetes reviews.

[49]  Andrea K. Chomistek,et al.  Television Watching , Leisure-Time Physical Activity and the Genetic Predisposition in Relation to Body Mass Index in Women and Men Running title : , 2012 .

[50]  N J Camp,et al.  Generating Genetic Risk Scores from Intermediate Phenotypes for Use in Association Studies of Clinically Significant Endpoints , 2005, Annals of human genetics.

[51]  Muin J Khoury,et al.  Evaluation of the discriminative accuracy of genomic profiling in the prediction of common complex diseases , 2010, European Journal of Human Genetics.

[52]  Bernard Keavney,et al.  Association of apolipoprotein E genotypes with lipid levels and coronary risk. , 2007, JAMA.

[53]  C. Stancu,et al.  Apolipoprotein E polymorphism – a risk factor for metabolic syndrome , 2007, Clinical chemistry and laboratory medicine.

[54]  Dolores Corella,et al.  Six new loci associated with blood low-density lipoprotein cholesterol, high-density lipoprotein cholesterol or triglycerides in humans , 2008, Nature Genetics.

[55]  A. Martí,et al.  Evidences on three relevant obesogenes: MC4R, FTO and PPARγ. Approaches for personalized nutrition. , 2011, Molecular nutrition & food research.

[56]  D. Strachan,et al.  LDL-cholesterol concentrations: a genome-wide association study , 2008, The Lancet.

[57]  D. A. Arias,et al.  Tables de Composicion de Alimentos , 1987 .

[58]  D. Belsky,et al.  Development and Evaluation of a Genetic Risk Score for Obesity , 2013, Biodemography and social biology.

[59]  P. Ridker,et al.  Lifestyle Interaction With Fat Mass and Obesity-Associated (FTO) Genotype and Risk of Obesity in Apparently Healthy U.S. Women , 2011, Diabetes Care.

[60]  D. Panagiotakos,et al.  Evidence for association between endothelial nitric oxide synthase gene polymorphism (G894T) and inflammatory markers: the ATTICA study. , 2004, American heart journal.

[61]  J. Martínez,et al.  The protein type within a hypocaloric diet affects obesity-related inflammation: the RESMENA project. , 2014, Nutrition.

[62]  Wolzt,et al.  World Medical Association Declaration of Helsinki: ethical principles for medical research involving human subjects. , 2003, The Journal of the American College of Dentists.

[63]  C. Bouchard,et al.  Advances in exercise, fitness, and performance genomics. , 2010, Medicine and science in sports and exercise.

[64]  E. Mariman,et al.  Relationship between perilipin gene polymorphisms and body weight and body composition during weight loss and weight maintenance , 2009, Physiology & Behavior.

[65]  J. Lind,et al.  Genetic discoveries in hypertension: steps on the road to therapeutic translation , 2013, Heart.

[66]  P. Rosch.  Risk of coronary artery disease. , 1983, JAMA.

[67]  Tanya M. Teslovich,et al.  Discovery and refinement of loci associated with lipid levels , 2013, Nature Genetics.

[68]  J. Martínez,et al.  A new dietary strategy for long-term treatment of the metabolic syndrome is compared with the American Heart Association (AHA) guidelines: the MEtabolic Syndrome REduction in NAvarra (RESMENA) project , 2013, British Journal of Nutrition.

[69]  K. Reynolds,et al.  Global burden of obesity in 2005 and projections to 2030 , 2008, International Journal of Obesity.

[70]  P. Wilson,et al.  Association Between the PPARA L162V Polymorphism and Plasma Lipid Levels: The Framingham Offspring Study , 2002, Arteriosclerosis, thrombosis, and vascular biology.

[71]  L. Qi.  Gene–diet interaction and weight loss , 2014, Current opinion in lipidology.

[72]  Jordi Salas-Salvadó,et al.  Consenso SEEDO 2007 para la evaluación del sobrepeso y la obesidad y el establecimiento de criterios de intervención terapéutica , 2007 .

[73]  P. Sham,et al.  Obesity susceptibility genetic variants identified from recent genome-wide association studies: implications in a chinese population. , 2010, The Journal of clinical endocrinology and metabolism.