{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,28]],"date-time":"2026-08-28T22:47:33Z","timestamp":1787957253034,"version":"build-2784847793"},"reference-count":87,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2021,6,13]],"date-time":"2021-06-13T00:00:00Z","timestamp":1623542400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Health Department of the Government of Navarra","award":["61\/2015"],"award-info":[{"award-number":["61\/2015"]}]},{"DOI":"10.13039\/100008666","name":"Fundaci\u00f3 la Marat\u00f3 de TV3","doi-asserted-by":"publisher","award":["201630.10"],"award-info":[{"award-number":["201630.10"]}],"id":[{"id":"10.13039\/100008666","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012514","name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red-Fisiopatolog\u00eda de la Obesidad y Nutrici\u00f3n","doi-asserted-by":"publisher","award":["CB12\/03\/3002"],"award-info":[{"award-number":["CB12\/03\/3002"]}],"id":[{"id":"10.13039\/501100012514","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Diagnostics"],"abstract":"<jats:p>Non-alcoholic fatty liver disease (NAFLD) affects 25% of the global population. The pathogenesis of NAFLD is complex; available data reveal that genetics and ascribed interactions with environmental factors may play an important role in the development of this morbid condition. The purpose of this investigation was to assess genetic and non-genetic determinants putatively involved in the onset and progression of NAFLD after a 6-month weight loss nutritional treatment. A group of 86 overweight\/obese subjects with NAFLD from the Fatty Liver in Obesity (FLiO) study were enrolled and metabolically evaluated at baseline and after 6 months. A pre-designed panel of 95 genetic variants related to obesity and weight loss was applied and analyzed. Three genetic risk scores (GRS) concerning the improvement on hepatic health evaluated by minimally invasive methods such as the fatty liver index (FLI) (GRSFLI), lipidomic-OWLiver\u00ae-test (GRSOWL) and magnetic resonance imaging (MRI) (GRSMRI), were derived by adding the risk alleles genotypes. Body composition, liver injury-related markers and dietary intake were also monitored. Overall, 23 SNPs were independently associated with the change in FLI, 16 SNPs with OWLiver\u00ae-test and 8 SNPs with MRI, which were specific for every diagnosis tool. After adjusting for gender, age and other related predictors (insulin resistance, inflammatory biomarkers and dietary intake at baseline) the calculated GRSFLI, GRSOWL and GRSMRI were major contributors of the improvement in hepatic status. Thus, fitted linear regression models showed a variance of 53% (adj. R2 = 0.53) in hepatic functionality (FLI), 16% (adj. R2 = 0.16) in lipidomic metabolism (OWLiver\u00ae-test) and 34% (adj. R2 = 0.34) in liver fat content (MRI). These results demonstrate that three different genetic scores can be useful for the personalized management of NAFLD, whose treatment must rely on specific dietary recommendations guided by the measurement of specific genetic biomarkers.<\/jats:p>","DOI":"10.3390\/diagnostics11061083","type":"journal-article","created":{"date-parts":[[2021,6,14]],"date-time":"2021-06-14T10:30:25Z","timestamp":1623666625000},"page":"1083","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Three Different Genetic Risk Scores Based on Fatty Liver Index, Magnetic Resonance Imaging and Lipidomic for a Nutrigenetic Personalized Management of NAFLD: The Fatty Liver in Obesity Study"],"prefix":"10.3390","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0479-8825","authenticated-orcid":false,"given":"Nuria","family":"Perez-Diaz-del-Campo","sequence":"first","affiliation":[{"name":"Department of Nutrition, Food Science and Physiology, Faculty of Pharmacy and Nutrition, University of Navarra, 31008 Pamplona, Spain"},{"name":"Centre for Nutrition Research, Faculty of Pharmacy and Nutrition, University of Navarra, 31008 Pamplona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1885-8457","authenticated-orcid":false,"given":"Jose I.","family":"Riezu-Boj","sequence":"additional","affiliation":[{"name":"Centre for Nutrition Research, Faculty of Pharmacy and Nutrition, University of Navarra, 31008 Pamplona, Spain"},{"name":"Navarra Institute for Health Research (IdiSNA), 31008 Pamplona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0741-8197","authenticated-orcid":false,"given":"Bertha Araceli","family":"Marin-Alejandre","sequence":"additional","affiliation":[{"name":"Department of Nutrition, Food Science and Physiology, Faculty of Pharmacy and Nutrition, University of Navarra, 31008 Pamplona, Spain"},{"name":"Centre for Nutrition Research, Faculty of Pharmacy and Nutrition, University of Navarra, 31008 Pamplona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J. Ignacio","family":"Monreal","sequence":"additional","affiliation":[{"name":"Navarra Institute for Health Research (IdiSNA), 31008 Pamplona, Spain"},{"name":"Clinical Chemistry Department, Cl\u00ednica Universidad de Navarra, 31008 Pamplona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1580-3629","authenticated-orcid":false,"given":"Mariana","family":"Elorz","sequence":"additional","affiliation":[{"name":"Navarra Institute for Health Research (IdiSNA), 31008 Pamplona, Spain"},{"name":"Department of Radiology, Cl\u00ednica Universidad de Navarra, 31008 Pamplona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jos\u00e9 Ignacio","family":"Herrero","sequence":"additional","affiliation":[{"name":"Navarra Institute for Health Research (IdiSNA), 31008 Pamplona, Spain"},{"name":"Liver Unit, Clinica Universidad de Navarra, 31008 Pamplona, Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Hep\u00e1ticas y Digestivas (CIBERehd), 28029 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alberto","family":"Benito-Boillos","sequence":"additional","affiliation":[{"name":"Navarra Institute for Health Research (IdiSNA), 31008 Pamplona, Spain"},{"name":"Department of Radiology, Cl\u00ednica Universidad de Navarra, 31008 Pamplona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3228-9916","authenticated-orcid":false,"given":"Ferm\u00edn I.","family":"Milagro","sequence":"additional","affiliation":[{"name":"Department of Nutrition, Food Science and Physiology, Faculty of Pharmacy and Nutrition, University of Navarra, 31008 Pamplona, Spain"},{"name":"Centre for Nutrition Research, Faculty of Pharmacy and Nutrition, University of Navarra, 31008 Pamplona, Spain"},{"name":"Navarra Institute for Health Research (IdiSNA), 31008 Pamplona, Spain"},{"name":"Biomedical Research Centre Network in Physiopathology of Obesity and Nutrition (CIBERobn), Instituto de Salud Carlos III, 28029 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6940-0761","authenticated-orcid":false,"given":"Josep A.","family":"Tur","sequence":"additional","affiliation":[{"name":"Biomedical Research Centre Network in Physiopathology of Obesity and Nutrition (CIBERobn), Instituto de Salud Carlos III, 28029 Madrid, Spain"},{"name":"Research Group on Community Nutrition and Oxidative Stress, Balearic Islands Institute for Health Research (IDISBA), University of Balearic Islands-IUNICS, 07122 Palma, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6475-5387","authenticated-orcid":false,"given":"Itziar","family":"Abete","sequence":"additional","affiliation":[{"name":"Department of Nutrition, Food Science and Physiology, Faculty of Pharmacy and Nutrition, University of Navarra, 31008 Pamplona, Spain"},{"name":"Centre for Nutrition Research, Faculty of Pharmacy and Nutrition, University of Navarra, 31008 Pamplona, Spain"},{"name":"Navarra Institute for Health Research (IdiSNA), 31008 Pamplona, Spain"},{"name":"Biomedical Research Centre Network in Physiopathology of Obesity and Nutrition (CIBERobn), Instituto de Salud Carlos III, 28029 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3926-0892","authenticated-orcid":false,"given":"M. Angeles","family":"Zulet","sequence":"additional","affiliation":[{"name":"Department of Nutrition, Food Science and Physiology, Faculty of Pharmacy and Nutrition, University of Navarra, 31008 Pamplona, Spain"},{"name":"Centre for Nutrition Research, Faculty of Pharmacy and Nutrition, University of Navarra, 31008 Pamplona, Spain"},{"name":"Navarra Institute for Health Research (IdiSNA), 31008 Pamplona, Spain"},{"name":"Biomedical Research Centre Network in Physiopathology of Obesity and Nutrition (CIBERobn), Instituto de Salud Carlos III, 28029 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5218-6941","authenticated-orcid":false,"given":"J. Alfredo","family":"Martinez","sequence":"additional","affiliation":[{"name":"Department of Nutrition, Food Science and Physiology, Faculty of Pharmacy and Nutrition, University of Navarra, 31008 Pamplona, Spain"},{"name":"Centre for Nutrition Research, Faculty of Pharmacy and Nutrition, University of Navarra, 31008 Pamplona, Spain"},{"name":"Navarra Institute for Health Research (IdiSNA), 31008 Pamplona, Spain"},{"name":"Biomedical Research Centre Network in Physiopathology of Obesity and Nutrition (CIBERobn), Instituto de Salud Carlos III, 28029 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,6,13]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1196","DOI":"10.1016\/j.jhep.2020.02.020","article-title":"Update on NAFLD Genetics: From New Variants to the Clinic","volume":"72","author":"Valenti","year":"2020","journal-title":"J. Hepatol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1016\/j.anndiagpath.2018.09.009","article-title":"Nonalcoholic Fatty Liver Disease (NAFLD): Diagnosis, Pitfalls, and Staging","volume":"37","author":"Koch","year":"2018","journal-title":"Ann. Diagn. Pathol."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Pais, R., and Maurel, T. (2021). Natural History of NAFLD. J. Clin. Med., 10.","DOI":"10.3390\/jcm10061161"},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Galarregui, C., Zulet, M.\u00c1., Cantero, I., Mar\u00edn-Alejandre, B.A., Monreal, J.I., Elorz, M., Benito-Boillos, A., Herrero, J.I., Tur, J.A., and Abete, I. (2018). Interplay of Glycemic Index, Glycemic Load, and Dietary Antioxidant Capacity with Insulin Resistance in Subjects with a Cardiometabolic Risk Profile. Int. J. Mol. Sci., 19.","DOI":"10.3390\/ijms19113662"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1586","DOI":"10.1016\/j.dld.2019.05.029","article-title":"Contribution of a Genetic Risk Score to Clinical Prediction of Hepatic Steatosis in Obese Children and Adolescents","volume":"51","author":"Zusi","year":"2019","journal-title":"Dig. Liver Dis."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Kup\u010dov\u00e1, V., Fedele\u0161ov\u00e1, M., Bulas, J., Kozmonov\u00e1, P., and Tureck\u00fd, L. (2019). Overview of the Pathogenesis, Genetic, and Non-Invasive Clinical, Biochemical, and Scoring Methods in the Assessment of NAFLD. Int. J. Environ. Res. Public Health, 16.","DOI":"10.3390\/ijerph16193570"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1111\/liv.13658","article-title":"Diagnosis of Non-Alcoholic Fatty Liver Disease\/Non-Alcoholic Steatohepatitis: Non-Invasive Tests Are Enough","volume":"38","author":"Castera","year":"2018","journal-title":"Liver Int."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"617","DOI":"10.1111\/apt.14219","article-title":"Serial Combination of Non-Invasive Tools Improves the Diagnostic Accuracy of Severe Liver Fibrosis in Patients with NAFLD","volume":"46","author":"Petta","year":"2017","journal-title":"Aliment. Pharmacol. Ther."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1521","DOI":"10.1111\/liv.14118","article-title":"Accuracy of Imaging Methods for Steatohepatitis Diagnosis in Non-Alcoholic Fatty Liver Disease Patients: A Systematic Review","volume":"39","author":"Besutti","year":"2019","journal-title":"Liver Int."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"902","DOI":"10.3945\/ajcn.117.156281","article-title":"Effect of the Interaction between Diet Composition and the PPM1K Genetic Variant on Insulin Resistance and \u03b2 Cell Function Markers during Weight Loss: Results from the Nutrient Gene Interactions in Human Obesity: Implications for Dietary Guidelines (NUGENOB) randomized trial","volume":"106","author":"Goni","year":"2017","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Perakakis, N., Polyzos, S.A., Yazdani, A., Sala-Vila, A., Kountouras, J., Anastasilakis, A.D., and Mantzoros, C.S. (2019). Non-Invasive Diagnosis of Non-Alcoholic Steatohepatitis and Fibrosis with the Use of Omics and Supervised Learning: A Proof of Concept Study. Metabolism, 101.","DOI":"10.1016\/j.metabol.2019.154005"},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Bedogni, G., Bellentani, S., Miglioli, L., Masutti, F., Passalacqua, M., Castiglione, A., and Tiribelli, C. (2006). The Fatty Liver Index: A Simple and Accurate Predictor of Hepatic Steatosis in the General Population. BMC Gastroenterol., 6.","DOI":"10.1186\/1471-230X-6-33"},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Murayama, K., Okada, M., Tanaka, K., Inadomi, C., Yoshioka, W., Kubotsu, Y., Yada, T., Isoda, H., Kuwashiro, T., and Oeda, S. (2021). Prediction of Nonalcoholic Fatty Liver Disease Using Noninvasive and Non-Imaging Procedures in Japanese Health Checkup Examinees. Diagnostics, 11.","DOI":"10.3390\/diagnostics11010132"},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Perez-Diaz-Del-Campo, N., Abete, I., Cantero, I., Marin-Alejandre, B.A., Monreal, J.I., Elorz, M., Herrero, J.I., Benito-Boillos, A., Riezu-Boj, J.I., and Milagro, F.I. (2020). Association of the SH2B1 RS7359397 Gene Polymorphism with Steatosis Severity in Subjects with Obesity and Non-Alcoholic Fatty Liver Disease. Nutrients, 12.","DOI":"10.3390\/nu12051260"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"178","DOI":"10.1016\/j.yexmp.2015.01.012","article-title":"A Genetic Risk Score Is Associated with Hepatic Triglyceride Content and Non-Alcoholic Steatohepatitis in Mexicans with Morbid Obesity","volume":"98","author":"Kauffer","year":"2015","journal-title":"Exp. Mol. Pathol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"845","DOI":"10.1002\/hep.31238","article-title":"Combined Effect of PNPLA3, TM6SF2, and HSD17B13 Variants on Risk of Cirrhosis and Hepatocellular Carcinoma in the General Population","volume":"72","author":"Richardson","year":"2020","journal-title":"Hepatology"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"671","DOI":"10.1038\/s41390-019-0303-1","article-title":"Genetic and Metabolic Predictors of Hepatic Fat Content in a Cohort of Italian Children with Obesity","volume":"85","author":"Pacifico","year":"2019","journal-title":"Pediatr. Res."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/s41598-019-39998-2","article-title":"Rare Pathogenic Variants Predispose to Hepatocellular Carcinoma in Nonalcoholic Fatty Liver Disease","volume":"9","author":"Pelusi","year":"2019","journal-title":"Sci. Rep."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1784","DOI":"10.1053\/j.gastro.2015.08.011","article-title":"Heritability of Hepatic Fibrosis and Steatosis Based on a Prospective Twin Study","volume":"149","author":"Loomba","year":"2015","journal-title":"Gastroenterology"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1912","DOI":"10.1002\/hep.31500","article-title":"Hepatic Fat\u2014Genetic Risk Score Predicts Hepatocellular Carcinoma in Patients with Cirrhotic HCV Treated with DAAs","volume":"72","author":"Degasperi","year":"2020","journal-title":"Hepatology"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1016\/S2213-8587(17)30200-0","article-title":"Genetics of Obesity: What Genetic Association Studies Have Taught Us about the Biology of Obesity and Its Complications","volume":"6","author":"Goodarzi","year":"2018","journal-title":"Lancet Diabetes Endocrinol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1002\/ncp.10449","article-title":"Evolution of NAFLD and Its Management","volume":"35","author":"Mundi","year":"2020","journal-title":"Nutr. Clin. Pract."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"3361","DOI":"10.3748\/wjg.v24.i30.3361","article-title":"Current Guidelines for the Management of Non-Alcoholic Fatty Liver Disease: A Systematic Review with Comparative Analysis","volume":"24","author":"Leoni","year":"2018","journal-title":"World J. Gastroenterol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1424","DOI":"10.1002\/hep.30782","article-title":"Report on the AASLD\/EASL Joint Workshop on Clinical Trial Endpoints in NAFLD","volume":"70","author":"Rinella","year":"2019","journal-title":"Hepatology"},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Abenavoli, L., Boccuto, L., Federico, A., Dallio, M., Loguercio, C., Di Renzo, L., and De Lorenzo, A. (2019). Diet and Non-Alcoholic Fatty Liver Disease: The Mediterranean Way. Int. J. Environ. Res. Public Health Rev., 16.","DOI":"10.3390\/ijerph16173011"},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Martinez, J.A., Navas-Carretero, S., Saris, W.H.M., and Astrup, A. (2014). Personalized Weight Loss Strategies\u2014The Role of Macronutrient Distribution. Nat. Rev. Endocrinol., 749\u2013760.","DOI":"10.1038\/nrendo.2014.175"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1175","DOI":"10.1001\/jama.2020.2298","article-title":"Nonalcoholic Steatohepatitis: A Review","volume":"323","author":"Sheka","year":"2020","journal-title":"JAMA J. Am. Med. Assoc."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"459","DOI":"10.1093\/ajcn\/nqz286","article-title":"Modeling of an Integrative Prototype Based on Genetic, Phenotypic, and Environmental Information for Personalized Prescription of Energy-Restricted Diets in Overweight\/Obese Subjects","volume":"111","author":"Cuervo","year":"2020","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"442","DOI":"10.1039\/D0FO02424D","article-title":"A Rational Review on the Effects of Sweeteners and Sweetness Enhancers on Appetite, Food Reward and Metabolic\/Adiposity Outcomes in Adults","volume":"12","author":"Pang","year":"2021","journal-title":"Food Funct."},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Gonz\u00e1lez-Muniesa, P., and Alfredo Mart\u00ednez, J. (2019). Precision Nutrition and Metabolic Syndrome Management. Nutrients, 11.","DOI":"10.3390\/nu11102411"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"305","DOI":"10.1038\/s41574-020-0346-8","article-title":"Contribution of Macronutrients to Obesity: Implications for Precision Nutrition","volume":"16","author":"Ordovas","year":"2020","journal-title":"Nat. Rev. Endocrinol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"75","DOI":"10.7150\/ijms.28044","article-title":"Ultrasound\/Elastography Techniques, Lipidomic and Blood Markers Compared to Magnetic Resonance Imaging in Non-Alcoholic Fatty Liver Disease Adults","volume":"16","author":"Cantero","year":"2019","journal-title":"Int. J. Med. Sci."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Marin-Alejandre, B.A., Abete, I., Cantero, I., Monreal, J.I., Martinez-echeverria, A., and Uriz-otano, J.I. (2019). The Metabolic and Hepatic Impact of Two Personalized Dietary Strategies in Subjects with Obesity and Nonalcoholic Fatty Liver Disease: The Fatty Liver in Obesity (FLiO) Randomized Controlled Trial. Nutrients, 11.","DOI":"10.3390\/nu11102543"},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Marin-Alejandre, B.A., Cantero, I., Perez-Diaz-del-Campo, N., Monreal, J.I., Elorz, M., Herrero, J.I., Benito-Boillos, A., Quiroga, J., Martinez-Echeverria, A., and Uriz-Otano, J.I. (2021). Effects of Two Personalized Dietary Strategies during a 2-year Intervention in Subjects with Nonalcoholic Fatty Liver Disease: A Randomized Trial. Liver Int.","DOI":"10.1111\/liv.14818"},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Perez-Diaz-del-Campo, N., Marin-Alejandre, B.A., Cantero, I., Monreal, J.I., Elorz, M., Herrero, J.I., Benito-Boillos, A., Riezu-Boj, J.I., Milagro, F.I., and Tur, J.A. (2021). Differential Response to a 6-Month Energy-Restricted Treatment Depending on SH2B1 Rs7359397 Variant in NAFLD Subjects: Fatty Liver in Obesity (FLiO) Study. Eur. J. Nutr.","DOI":"10.1007\/s00394-020-02476-x"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"344","DOI":"10.1002\/hep.24376","article-title":"Endpoints and Clinical Trial Design for Nonalcoholic Steatohepatitis","volume":"54","author":"Sanyal","year":"2011","journal-title":"Hepatology"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"328","DOI":"10.1002\/hep.29367","article-title":"The Diagnosis and Management of Nonalcoholic Fatty Liver Disease: Practice Guidance from the American Association for the Study of Liver Diseases","volume":"67","author":"Chalasani","year":"2018","journal-title":"Hepatology"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1808","DOI":"10.1017\/S0007114509993837","article-title":"Relative Validity of a Semi-Quantitative Food-Frequency Questionnaire in an Elderly Mediterranean Population of Spain","volume":"103","author":"Zazpe","year":"2010","journal-title":"Br. J. Nutr."},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Galarregui, C., Marin-Alejandre, B.A., Perez-Diaz-Del-Campo, N., Cantero, I., Monreal, J.I., Elorz, M., Benito-Boillos, A., Herrero, J.I., Tur, J.A., and Mart\u00ednez, J.A. (2020). Predictive Value of Serum Ferritin in Combination with Alanine Aminotransferase and Glucose Levels for Noninvasive Assessment of NAFLD: Fatty Liver in Obesity (FLiO) Study. Diagnostics, 10.","DOI":"10.3390\/diagnostics10110917"},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Recaredo, G., Marin-Alejandre, B.A., Cantero, I., Monreal, J.I., Herrero, J.I., Benito-Boillos, A., Elorz, M., Tur, J.A., Mart\u00ednez, J.A., and Zulet, M.A. (2019). Association between Different Animal Protein Sources and Liver Status in Obese Subjects with Non-Alcoholic Fatty Liver Disease: Fatty Liver in Obesity (FLiO) Study. Nutrients, 11.","DOI":"10.3390\/nu11102359"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"387","DOI":"10.1093\/ije\/dyy225","article-title":"Cohort Profile: Design and Methods of the PREDIMED-Plus Randomized Trial","volume":"48","author":"Corella","year":"2019","journal-title":"Int. J. Epidemiol."},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Galmes-Panades, A.M., Konieczna, J., Abete, I., Colom, A., Rosique-Esteban, N., Zulet, M.A., V\u00e1zquez, Z., Estruch, R., Vidal, J., and Toledo, E. (2019). Lifestyle Factors and Visceral Adipose Tissue: Results from the PREDIMED-PLUS Study. PLoS ONE, 14.","DOI":"10.1371\/journal.pone.0210726"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1431","DOI":"10.1097\/00005768-200008000-00011","article-title":"Validation of the Minnesota Leisure Time Spanish Women","volume":"32","author":"Elosua","year":"2000","journal-title":"Med. Sci. Sport. Exerc."},{"key":"ref_44","first-page":"1197","article-title":"Validation of the Minnesota Leisure Time Physical Activity Questionnaire in Spanish Men","volume":"139","author":"Elosua","year":"1994","journal-title":"Med. Sci. Sports Exerc."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"643","DOI":"10.1017\/S0007114513002778","article-title":"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","volume":"111","author":"Abete","year":"2014","journal-title":"Br. J. Nutr."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1016\/j.ypmed.2016.01.022","article-title":"Triglyceride-Glucose Index (TyG Index) in Comparison with Fasting Plasma Glucose Improved Diabetes Prediction in Patients with Normal Fasting Glucose: The Vascular-Metabolic CUN Cohort","volume":"86","author":"Martinez","year":"2016","journal-title":"Prev. Med."},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Marin-Alejandre, B.A., Abete, I., Cantero, I., Riezu-Boj, J.I., Milagro, F.I., Monreal, J.I., Elorz, M., Herrero, J.I., Benito-Boillos, A., and Quiroga, J. (2019). Association between Sleep Disturbances and Liver Status in Obese Subjects with Nonalcoholic Fatty Liver Disease: A Comparison with Healthy Controls. Nutrients, 11.","DOI":"10.3390\/nu11020322"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"7392","DOI":"10.3748\/wjg.v20.i23.7392","article-title":"Radiologic Evaluation of Nonalcoholic Fatty Liver Disease","volume":"20","author":"Lee","year":"2014","journal-title":"World J. Gastroenterol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1702","DOI":"10.1111\/dom.13285","article-title":"Use of a Metabolomic Approach to Non-Invasively Diagnose Non-Alcoholic Fatty Liver Disease in Patients with Type 2 Diabetes Mellitus","volume":"20","author":"Bril","year":"2018","journal-title":"Diabetes, Obes. Metab."},{"key":"ref_50","first-page":"43","article-title":"Guide for Current Nutrigenetic, Nutrigenomic, and Nutriepigenetic Approaches for Precision Nutrition Involving the Prevention and Management of Chronic Diseases Associated with Obesity","volume":"10","author":"Milagro","year":"2017","journal-title":"J. Nutrigenet. Nutr."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1909","DOI":"10.2337\/dc16-1111","article-title":"Macronutrient Intake-Associated FGF21 Genotype Modifies Effects of Weight-Loss Diets on 2-Year Changes of Central Adiposity and Body Composition: The POUNDS Lost Trial","volume":"39","author":"Heianza","year":"2016","journal-title":"Diabetes Care"},{"key":"ref_52","first-page":"232","article-title":"Gene-Gene Interplay and Gene-Diet Interactions Involving the MTNR1B Rs10830963 Variant with Body Weight Loss","volume":"7","author":"Goni","year":"2015","journal-title":"J. Nutrigenet. Nutrigenom."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1016\/j.fsigen.2016.07.021","article-title":"Next Generation Sequencing of SNPs Using the HID-Ion AmpliSeqTM Identity Panel on the Ion Torrent PGMTM Platform","volume":"25","author":"Guo","year":"2016","journal-title":"Forensic Sci. Int. Genet."},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Ramos-Lopez, O., Riezu-Boj, J.I., Milagro, F.I., Cuervo, M., Goni, L., and Martinez, J.A. (2018). Prediction of Blood Lipid Phenotypes Using Obesity-Related Genetic Polymorphisms and Lifestyle Data in Subjects with Excessive Body Weight. Int. J. Genom., 2018.","DOI":"10.1155\/2018\/4283078"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"686","DOI":"10.3389\/fgene.2019.00686","article-title":"Models Integrating Genetic and Lifestyle Interactions on Two Adiposity Phenotypes for Personalized Prescription of Energy-Restricted Diets with Different Macronutrient Distribution","volume":"10","author":"Milagro","year":"2019","journal-title":"Front. Genet."},{"key":"ref_56","doi-asserted-by":"crossref","unstructured":"Cuevas-Sierra, A., Riezu-Boj, J.I., Guruceaga, E., Milagro, F.I., and Mart\u00ednez, J.A. (2020). Sex-Specific Associations between Gut Prevotellaceae and Host Genetics on Adiposity. Microorganisms, 8.","DOI":"10.3390\/microorganisms8060938"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1038\/nrgastro.2017.109","article-title":"Global Burden of NAFLD and NASH: Trends, Predictions, Risk Factors and Prevention","volume":"15","author":"Younossi","year":"2018","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1007\/s00018-018-2947-0","article-title":"Molecular Pathways of Nonalcoholic Fatty Liver Disease Development and Progression","volume":"76","author":"Bessone","year":"2019","journal-title":"Cell. Mol. Life Sci."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"511","DOI":"10.4239\/wjd.v5.i4.511","article-title":"SH2B1 Regulation of Energy Balance, Body Weight, and Glucose Metabolism","volume":"5","author":"Rui","year":"2014","journal-title":"World J. Diabetes"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"505","DOI":"10.1016\/j.jhep.2020.04.003","article-title":"Genome-Wide Association Study of Non-Alcoholic Fatty Liver and Steatohepatitis in a Histologically Characterised Cohort","volume":"73","author":"Anstee","year":"2020","journal-title":"J. Hepatol."},{"key":"ref_61","doi-asserted-by":"crossref","unstructured":"Younossi, Z., Tacke, F., Arrese, M., Chander Sharma, B., Mostafa, I., Bugianesi, E., Wai-Sun Wong, V., Yilmaz, Y., George, J., and Fan, J. (2019). Global Perspectives on Nonalcoholic Fatty Liver Disease and Nonalcoholic Steatohepatitis. Hepatology, John Wiley and Sons Inc.","DOI":"10.1002\/hep.30251"},{"key":"ref_62","doi-asserted-by":"crossref","unstructured":"Kabisch, S., B\u00e4ther, S., Dambeck, U., Kemper, M., Gerbracht, C., Honsek, C., Sachno, A., and Pfeiffer, A.F.H. (2018). Liver Fat Scores Moderately Reflect Interventional Changes in Liver Fat Content by a Low-Fat Diet but Not by a Low-Carb Diet. Nutrients, 10.","DOI":"10.3390\/nu10020157"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"E253","DOI":"10.1097\/MCG.0000000000001089","article-title":"Both WHR and FLI as Better Algorithms for Both Lean and Overweight\/Obese NAFLD in a Chinese Population","volume":"53","author":"Li","year":"2019","journal-title":"J. Clin. Gastroenterol."},{"key":"ref_64","doi-asserted-by":"crossref","unstructured":"Karlas, T., Petroff, D., Garnov, N., B\u00f6hm, S., Tenckhoff, H., Wittekind, C., Wiese, M., Schiefke, I., Linder, N., and Schaudinn, A. (2014). Non-Invasive Assessment of Hepatic Steatosis in Patients with NAFLD Using Controlled Attenuation Parameter and 1H-MR Spectroscopy. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0091987"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"807","DOI":"10.1002\/hep4.1188","article-title":"Metabolomic-based Noninvasive Serum Test to Diagnose Nonalcoholic Steatohepatitis: Results from Discovery and Validation Cohorts","volume":"2","author":"Mayo","year":"2018","journal-title":"Hepatol. Commun."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"1924","DOI":"10.1038\/oby.2009.199","article-title":"PPARG Genotype Accounts for Part of Individual Variation in Body Weight Reduction in Response to Calorie Restriction","volume":"17","author":"Matsuo","year":"2009","journal-title":"Obesity"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"1088","DOI":"10.1111\/dom.13641","article-title":"Obesity Genetics and Cardiometabolic Health: Potential for Risk Prediction","volume":"21","author":"Sanghera","year":"2019","journal-title":"Diabetes, Obes. Metab."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1038\/nature14177","article-title":"Genetic Studies of Body Mass Index Yield New Insights for Obesity Biology","volume":"518","author":"Locke","year":"2015","journal-title":"Nature"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"1761","DOI":"10.1038\/ijo.2017.169","article-title":"Dietary Fat and Total Energy Intake Modifies the Association of Genetic Profile Risk Score on Obesity: Evidence from 48170 UK Biobank Participants","volume":"41","author":"Lyall","year":"2017","journal-title":"Int. J. Obes."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"485","DOI":"10.1038\/ejhg.2009.209","article-title":"Evaluation of the Discriminative Accuracy of Genomic Profiling in the Prediction of Common Complex Diseases","volume":"18","author":"Moonesinghe","year":"2010","journal-title":"Eur. J. Hum. Genet."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"E1","DOI":"10.1097\/TP.0000000000002480","article-title":"Nonalcoholic Fatty Liver Disease: Basic Pathogenetic Mechanisms in the Progression from NAFLD to NASH","volume":"103","author":"Pierantonelli","year":"2019","journal-title":"Transplantation"},{"key":"ref_72","doi-asserted-by":"crossref","unstructured":"Tucker, B., Li, H., Long, X., Rye, K.A., and Ong, K.L. (2019). Fibroblast Growth Factor 21 in Non-Alcoholic Fatty Liver Disease. Metab. Clin. Exp.","DOI":"10.1016\/j.metabol.2019.153994"},{"key":"ref_73","doi-asserted-by":"crossref","unstructured":"Cantero, I., Abete, I., Monreal, J.I., Martinez, J.A., and Zulet, M.A. (2017). Fruit Fiber Consumption Specifically Improves Liver Health Status in Obese Subjects under Energy Restriction. Nutrients, 9.","DOI":"10.3390\/nu9070667"},{"key":"ref_74","first-page":"620","article-title":"Influence of Lifestyle Factors and Staple Foods from the Mediterranean Diet on Non-Alcoholic Fatty Liver Disease among Older Individuals with Metabolic Syndrome Features","volume":"71","author":"Abete","year":"2020","journal-title":"Nutrition"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"1387","DOI":"10.1056\/NEJMoa1203039","article-title":"Sugar-Sweetened Beverages and Genetic Risk of Obesity","volume":"367","author":"Qi","year":"2012","journal-title":"N. Engl. J. Med."},{"key":"ref_76","doi-asserted-by":"crossref","unstructured":"Rask-Andersen, M., Karlsson, T., Ek, W.E., and Johansson, \u00c5. (2017). Gene-Environment Interaction Study for BMI Reveals Interactions between Genetic Factors and Physical Activity, Alcohol Consumption and Socioeconomic Status. PLoS Genet., 13.","DOI":"10.1371\/journal.pgen.1006977"},{"key":"ref_77","first-page":"25","article-title":"Gene-Environment Interactions and the Genetic Epidemiology of Obesity: Correlates for Preventative Medicine","volume":"1","author":"Mangum","year":"2018","journal-title":"SSRN Electron. J."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"2467","DOI":"10.2337\/db14-1629","article-title":"Dietary Intake, FTO Genetic Variants, and Adiposity: A Combined Analysis of over 16,000 Children and Adolescents","volume":"64","author":"Qi","year":"2015","journal-title":"Diabetes"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1093\/ajcn\/nqz035","article-title":"Effects of Red Meat, White Meat, and Nonmeat Protein Sources on Atherogenic Lipoprotein Measures in the Context of Low Compared with High Saturated Fat Intake: A Randomized Controlled Trial","volume":"110","author":"Bergeron","year":"2019","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"240","DOI":"10.1080\/09637486.2018.1492524","article-title":"Higher Vegetable Protein Consumption, Assessed by an Isoenergetic Macronutrient Exchange Model, Is Associated with a Lower Presence of Overweight and Obesity in the Web-Based Food4me European Study","volume":"70","author":"Livingstone","year":"2019","journal-title":"Int. J. Food Sci. Nutr."},{"key":"ref_81","doi-asserted-by":"crossref","unstructured":"Galarregui, C., Cantero, I., Marin-Alejandre, B.A., Monreal, J.I., Elorz, M., Benito-Boillos, A., Herrero, J.I., de la O, V., Ruiz-Canela, M., and Hermsdorff, H.H.M. (2020). Dietary Intake of Specific Amino Acids and Liver Status in Subjects with Nonalcoholic Fatty Liver Disease: Fatty Liver in Obesity (FLiO) Study. Eur. J. Nutr.","DOI":"10.1007\/s00394-020-02370-6"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"606","DOI":"10.1016\/j.cmet.2012.01.024","article-title":"Interplay between Lipids and Branched-Chain Amino Acids in Development of Insulin Resistance","volume":"15","author":"Newgard","year":"2012","journal-title":"Cell Metab."},{"key":"ref_83","doi-asserted-by":"crossref","unstructured":"Alsulami, S., Aji, A.S., Ariyasra, U., Sari, S.R., Tasrif, N., Yani, F.F., Lovegrove, J.A., Sudji, I.R., Lipoeto, N.I., and Vimaleswaran, K.S. (2020). Interaction between the Genetic Risk Score and Dietary Protein Intake on Cardiometabolic Traits in Southeast Asian. Genes Nutr., 15.","DOI":"10.1186\/s12263-020-00678-w"},{"key":"ref_84","doi-asserted-by":"crossref","unstructured":"De Chiara, F., Checcllo, C.U., and Azc\u00f3n, J.R. (2019). High Protein Diet and Metabolic Plasticity in Non-Alcoholic Fatty Liver Disease: Myths and Truths. Nutrients, 11.","DOI":"10.3390\/nu11122985"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1016\/j.metabol.2016.12.013","article-title":"Branched-Chain Amino Acids Alleviate Hepatic Steatosis and Liver Injury in Choline-Deficient High-Fat Diet Induced NASH Mice","volume":"69","author":"Honda","year":"2017","journal-title":"Metabolism"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"18191","DOI":"10.18632\/oncotarget.15304","article-title":"Branched-Chain Amino Acids Prevent Hepatic Fibrosis and Development of Hepatocellular Carcinoma in a Non-Alcoholic Steatohepatitis Mouse Model","volume":"8","author":"Takegoshi","year":"2017","journal-title":"Oncotarget"},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"1068","DOI":"10.1111\/jcpp.12295","article-title":"Research Review: Polygenic Methods and Their Application to Psychiatric Traits","volume":"55","author":"Wray","year":"2014","journal-title":"J. Child Psychol. Psychiatry Allied Discip."}],"container-title":["Diagnostics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2075-4418\/11\/6\/1083\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T06:13:54Z","timestamp":1760163234000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2075-4418\/11\/6\/1083"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,6,13]]},"references-count":87,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2021,6]]}},"alternative-id":["diagnostics11061083"],"URL":"https:\/\/doi.org\/10.3390\/diagnostics11061083","relation":{"has-preprint":[{"id-type":"doi","id":"10.21203\/rs.3.rs-333145\/v1","asserted-by":"object"}]},"ISSN":["2075-4418"],"issn-type":[{"value":"2075-4418","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,6,13]]}}}