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Metabolic Syndrome Prediction Using Machine Learning Models with Genetic and Clinical Information from a Nonobese Healthy Population

  • Received : 2018.11.13
  • Accepted : 2018.12.03
  • Published : 2018.12.31

Abstract

The prevalence of metabolic syndrome (MS) in the nonobese population is not low. However, the identification and risk mitigation of MS are not easy in this population. We aimed to develop an MS prediction model using genetic and clinical factors of nonobese Koreans through machine learning methods. A prediction model for MS was designed for a nonobese population using clinical and genetic polymorphism information with five machine learning algorithms, including naïve Bayes classification (NB). The analysis was performed in two stages (training and test sets). Model A was designed with only clinical information (age, sex, body mass index, smoking status, alcohol consumption status, and exercise status), and for model B, genetic information (for 10 polymorphisms) was added to model A. Of the 7,502 nonobese participants, 647 (8.6%) had MS. In the test set analysis, for the maximum sensitivity criterion, NB showed the highest sensitivity: 0.38 for model A and 0.42 for model B. The specificity of NB was 0.79 for model A and 0.80 for model B. In a comparison of the performances of models A and B by NB, model B (area under the receiver operating characteristic curve [AUC] = 0.69, clinical and genetic information input) showed better performance than model A (AUC = 0.65, clinical information only input). We designed a prediction model for MS in a nonobese population using clinical and genetic information. With this model, we might convince nonobese MS individuals to undergo health checks and adopt behaviors associated with a preventive lifestyle.

Keywords

References

  1. O'Neill S, O'Driscoll L. Metabolic syndrome: a closer look at the growing epidemic and its associated pathologies. Obes Rev 2015;16:1-12.
  2. Sookoian S, Pirola CJ. Metabolic syndrome: from the genetics to the pathophysiology. Curr Hypertens Rep 2011;13:149-157. https://doi.org/10.1007/s11906-010-0164-9
  3. Drager LF, Togeiro SM, Polotsky VY, Lorenzi-Filho G. Obstructive sleep apnea: a cardiometabolic risk in obesity and the metabolic syndrome. J Am Coll Cardiol 2013;62:569-576. https://doi.org/10.1016/j.jacc.2013.05.045
  4. Yki-Jarvinen H. Non-alcoholic fatty liver disease as a cause and a consequence of metabolic syndrome. Lancet Diabetes Endocrinol 2014;2:901-910. https://doi.org/10.1016/S2213-8587(14)70032-4
  5. Esposito K, Chiodini P, Capuano A, Bellastella G, Maiorino MI, Rafaniello C, et al. Colorectal cancer association with metabolic syndrome and its components: a systematic review with meta-analysis. Endocrine 2013;44:634-647. https://doi.org/10.1007/s12020-013-9939-5
  6. Argolo DF, Hudis CA, Iyengar NM. The impact of obesity on breast cancer. Curr Oncol Rep 2018;20:47. https://doi.org/10.1007/s11912-018-0688-8
  7. Ni J, Zhu T, Zhao L, Che F, Chen Y, Shou H, et al. Metabolic syndrome is an independent prognostic factor for endometrial adenocarcinoma. Clin Transl Oncol 2015;17:835-839. https://doi.org/10.1007/s12094-015-1309-8
  8. Esposito K, Chiodini P, Capuano A, Bellastella G, Maiorino MI, Giugliano D. Metabolic syndrome and endometrial cancer: a meta-analysis. Endocrine 2014;45:28-36. https://doi.org/10.1007/s12020-013-9973-3
  9. Gacci M, Russo GI, De Nunzio C, Sebastianelli A, Salvi M, Vignozzi L, et al. Meta-analysis of metabolic syndrome and prostate cancer. Prostate Cancer Prostatic Dis 2017;20:146-155. https://doi.org/10.1038/pcan.2017.1
  10. Mendonca FM, de Sousa FR, Barbosa AL, Martins SC, Araujo RL, Soares R, et al. Metabolic syndrome and risk of cancer: which link? Metabolism 2015;64:182-189. https://doi.org/10.1016/j.metabol.2014.10.008
  11. Despres JP, Lemieux I. Abdominal obesity and metabolic syndrome. Nature 2006;444:881-887. https://doi.org/10.1038/nature05488
  12. Eftekharzadeh A, Asghari G, Serahati S, Hosseinpanah F, Azizi A, Barzin M, et al. Predictors of incident obesity phenotype in nonobese healthy adults. Eur J Clin Invest 2017;47:357-365. https://doi.org/10.1111/eci.12743
  13. Kraja AT, Vaidya D, Pankow JS, Goodarzi MO, Assimes TL, Kullo IJ, et al. A bivariate genome-wide approach to metabolic syndrome: STAMPEED consortium. Diabetes 2011;60:1329-1339. https://doi.org/10.2337/db10-1011
  14. Spracklen CN, Chen P, Kim YJ, Wang X, Cai H, Li S, et al. Association analyses of East Asian individuals and trans-ancestry analyses with European individuals reveal new loci associated with cholesterol and triglyceride levels. Hum Mol Genet 2017;26:1770-1784. https://doi.org/10.1093/hmg/ddx062
  15. Kristiansson K, Perola M, Tikkanen E, Kettunen J, Surakka I, Havulinna AS, et al. Genome-wide screen for metabolic syndrome susceptibility Loci reveals strong lipid gene contribution but no evidence for common genetic basis for clustering of metabolic syndrome traits. Circ Cardiovasc Genet 2012;5:242-249. https://doi.org/10.1161/CIRCGENETICS.111.961482
  16. Coram MA, Duan Q, Hoffmann TJ, Thornton T, Knowles JW, Johnson NA, et al. Genome-wide characterization of shared and distinct genetic components that influence blood lipid levels in ethnically diverse human populations. Am J Hum Genet 2013;92:904-916. https://doi.org/10.1016/j.ajhg.2013.04.025
  17. Surakka I, Horikoshi M, Magi R, Sarin AP, Mahajan A, Lagou V, et al. The impact of low-frequency and rare variants on lipid levels. Nat Genet 2015;47:589-597. https://doi.org/10.1038/ng.3300
  18. Comuzzie AG, Cole SA, Laston SL, Voruganti VS, Haack K, Gibbs RA, et al. Novel genetic loci identified for the pathophysiology of childhood obesity in the Hispanic population. PLoS One 2012;7:e51954. https://doi.org/10.1371/journal.pone.0051954
  19. Sabatti C, Service SK, Hartikainen AL, Pouta A, Ripatti S, Brodsky J, et al. Genome-wide association analysis of metabolic traits in a birth cohort from a founder population. Nat Genet 2009;41:35-46. https://doi.org/10.1038/ng.271
  20. Fox CS, Liu Y, White CC, Feitosa M, Smith AV, Heard-Costa N, et al. Genome-wide association for abdominal subcutaneous and visceral adipose reveals a novel locus for visceral fat in women. PLoS Genet 2012;8:e1002695. https://doi.org/10.1371/journal.pgen.1002695
  21. Guarner V, Rubio-Ruiz ME. Low-grade systemic inflammation connects aging, metabolic syndrome and cardiovascular disease. Interdiscip Top Gerontol 2015;40:99-106.
  22. Rochlani Y, Pothineni NV, Mehta JL. Metabolic syndrome: does it differ between women and men? Cardiovasc Drugs Ther 2015;29:329-338. https://doi.org/10.1007/s10557-015-6593-6
  23. Pitsavos C, Panagiotakos D, Weinem M, Stefanadis C. Diet, exercise and the metabolic syndrome. Rev Diabet Stud 2006;3:118-126. https://doi.org/10.1900/RDS.2006.3.118
  24. Sun K, Ren M, Liu D, Wang C, Yang C, Yan L. Alcohol consumption and risk of metabolic syndrome: a meta-analysis of prospective studies. Clin Nutr 2014;33:596-602. https://doi.org/10.1016/j.clnu.2013.10.003
  25. Shin HS, Oh JE, Cho YJ. The association between smoking cessation period and metabolic syndrome in Korean men. Asia Pac J Public Health 2018;30:415-424. https://doi.org/10.1177/1010539518786517
  26. Lee C, Choe EK, Choi JM, Hwang Y, Lee Y, Park B, et al. Health and Prevention Enhancement (H-PEACE): a retrospective, population-based cohort study conducted at the Seoul National University Hospital Gangnam Center, Korea. BMJ Open 2018;8:e019327. https://doi.org/10.1136/bmjopen-2017-019327
  27. Alberti KG, Zimmet P, Shaw J; IDF Epidemiology Task Force Consensus Group. The metabolic syndrome: a new worldwide definition. Lancet 2005;366: 1059-1062. https://doi.org/10.1016/S0140-6736(05)67402-8
  28. Tafeit E, Reibnegger G. Artificial neural networks in laboratory medicine and medical outcome prediction. Clin Chem Lab Med 1999;37:845-853.
  29. Abdo A, Chen B, Mueller C, Salim N, Willett P. Ligand-based virtual screening using Bayesian networks. J Chem Inf Model 2010;50:1012-1020. https://doi.org/10.1021/ci100090p
  30. Plewczynski D, von Grotthuss M, Rychlewski L, Ginalski K. Virtual high throughput screening using combined random forest and flexible docking. Comb Chem High Throughput Screen 2009;12:484-489. https://doi.org/10.2174/138620709788489000
  31. Che D, Hockenbury C, Marmelstein R, Rasheed K. Classification of genomic islands using decision trees and their ensemble algorithms. BMC Genomics 2010;11 Suppl 2:S1.
  32. Jorissen RN, Gilson MK. Virtual screening of molecular databases using a support vector machine. J Chem Inf Model 2005;45:549-561. https://doi.org/10.1021/ci049641u
  33. Malnick SD, Knobler H. The medical complications of obesity. QJM 2006;99:565-579. https://doi.org/10.1093/qjmed/hcl085
  34. Nguyen DM, El-Serag HB. The epidemiology of obesity. Gastroenterol Clin North Am 2010;39:1-7. https://doi.org/10.1016/j.gtc.2009.12.014
  35. Pajunen P, Kotronen A, Korpi-Hyovalti E, Keinanen- Kiukaanniemi S, Oksa H, Niskanen L, et al. Metabolically healthy and unhealthy obesity phenotypes in the general population: the FIN-D2D Survey. BMC Public Health 2011;11:754. https://doi.org/10.1186/1471-2458-11-754
  36. Phillips CM, Perry IJ. Does inflammation determine metabolic health status in obese and nonobese adults? J Clin Endocrinol Metab 2013;98:E1610-E1619. https://doi.org/10.1210/jc.2013-2038
  37. Bo S, Ciccone G, Pearce N, Merletti F, Gentile L, Cassader M, et al. Prevalence of undiagnosed metabolic syndrome in a population of adult asymptomatic subjects. Diabetes Res Clin Pract 2007;75:362-365. https://doi.org/10.1016/j.diabres.2006.06.031
  38. Blanco R, Inza I, Merino M, Quiroga J, Larranaga P. Feature selection in Bayesian classifiers for the prognosis of survival of cirrhotic patients treated with TIPS. J Biomed Inform 2005;38:376-388. https://doi.org/10.1016/j.jbi.2005.05.004
  39. Sandberg R, Winberg G, Branden CI, Kaske A, Ernberg I, Coster J. Capturing whole-genome characteristics in short sequences using a naive Bayesian classifier. Genome Res 2001;11:1404-1409. https://doi.org/10.1101/gr.186401
  40. Zelic I, Kononenko I, Lavrac N, Vuga V. Induction of decision trees and Bayesian classification applied to diagnosis of sport injuries. J Med Syst 1997;21:429-444. https://doi.org/10.1023/A:1022880431298