ABC | Volume 111, Nº1, July 2018

Original Article Pereira et al. Genes and coronary artery disease risk Arq Bras Cardiol. 2018; 111(1):50-61 1. Lawrence C, Boerwinkle E. Gene-environment interactions and gene therapy in atherosclerosis . Cardiol Rev. 1994;2:130-7. 2. Wellcome Trust Case Control Consortium. Genome-wide association study of 14,000 cases of seven common diseases and 3,000 shared controls. Nature. 2007; 447(7145):661-78. 3. Myocardial infarctionredefined.AconsensusdocumentoftheJointEuropean Society of Cardiology/American College of Cardiology Committee for the redefinition of myocardial infarction. Eur Heart J. 2000;21(18):1502-13. 4. Abdi H, Williams LJ. Principal component analysis. WIREs Computacional Statistics. 2010;2:433-59. 5. Mons U, Müezzinler A, Gellert C, Schöttker B, Abnet CC, Bobak M, et al; CHANCES Consortium. Impact of smoking and smoking cessation on cardiovascular events and mortality among older adults: meta-analysis of individual participant data fromprospective cohort studies of the CHANCES consortium. BMJ. 2015;350:h1551. 6. Chobanian AV, Bakris GL, Black HR, Cushman WC, Green LA, Izzo JL Jr, et al; National Heart, Lung, and Blood Institute Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure; National High Blood Pressure Education ProgramCoordinating Committee. The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation and Treatment of High Blood Pressure: the JNC 7 report. JAMA. 2003;289(19):2560-72. Erratum in: JAMA. 2003;290(2):197. 7. Expert Panel on Detection Evaluation and Treatment of High Blood Cholesterol in Adults. Executive Summary of the Third Report of the National Cholesterol Education Program (NCEPT) Expert Panel onDetection Evaluation and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III). JAMA. 2001;285(19):2486-97. 8. Genuth S, Alberti KG, Bennett P, Buse J, Defronzo R, Kahn R, et al; Expert Committee on the Diagnosis and Classification of Diabetes Mellitus. Follow-up reportonthediagnosisofdiabetesmellitus.DiabetesCare.2003;26(11):3160-7. 9. National Institute of Health, National Heart, Lung, and Blood Institute North AmericanAssociationfortheStudyofObesity.ThePracticalGuide:Identification, Evaluation,andTreatmentofOverweightandObesity inAdults.NHLBIObesity EducationInitiative.Bethesda(MD);2000.NIHPublicationNumber:00-4084. 10. Asmar R, Benetos A, Topouchian J, Laurent P, Pannier B, Brisac AM, et al. Assessment of arterial distensibility by automatic pulse wave velocity measurement: validation and clinical application studies. Hypertension. 1995;26(3):485-90. 11. DeLong ER, DeLong DM, Clarke-Pearson DL. Comparing the areas under two or more correlated receiver operating characteristic curves: a nonparametric approach. Biometrics. 1988;44(3):837-45. 12. Pencina MJ, D’Agostino RB Sr, Steyerberg EW. Extensions of net reclassification improvement calculations to measure usefulness of new biomarkers. Stat Med. 2011;30(1):11-21. 13. Humphries SE, Morgan L. Genetic risk factors for stroke and carotid atherosclerosis: insights into pathophysiology from candidate gene approaches. Lancet Neurol. 2004;3(4):227-35. 14. Mendonça I, Freitas AI, Sousa AC, Gomes S, Faria P, Drumond A, et al. Polymorphism of the ACE gene is associated with extent and severity of coronary disease. Rev Port Cardiol 2004;23(12):1605-11. 15. Keating BJ, Tischfield S, Murray SS, Bhangale T, Price TS, Glessner JT, et al. Concept,designandimplementationofacardiovasculargene-centric50kSNP arrayforlarge-scalegenomicassociationstudies.PLoSOne.2008;3(10):e3583. 16. McCarthy MI, Abecasis GR, Cardon LR, Goldstein DB, Little J, Ioannidis JP, et al. Genome-wide association studies for complex traits: consensus, uncertainty and challenges. Nat Rev Genet. 2008;9(5):356-69. 17. Samani NJ, Erdmann J, Hall AS, Hengstenberg C, Mangino M, Mayer B, et al; WTCCC and the Cardiogenics Consortium. Genomewide association analysis of coronary artery disease. N Engl J Med 2007;357(5):443-53. 18. Preuss M, König IR, Thompson JR, Erdman J, Absher D, Assimes TL, et al; CARDIoGRAM Consortium. Design of the Coronary ARtery DIsease Genome-Wide Replication And Meta-Analysis (CARDIoGRAM) Study: A Genome-wide association meta-analysis involving more than 22 000 cases and 60 000 controls. Circ Cardiovasc Genet. 2010;3(5):475-83. 19. MendonçaI,dosReisRP,PereiraA,CaféH,SerrãoM,SousaAC,etal.Associação independentedavarianters1333049,no locus9p21,comadoençacoronária, numa população portuguesa. Rev Port Cardiol. 2011;30(6):575-91. References 2.5 times increased CAD risk when compared to those in the lowest quartile. This GRS has provided a slight improvement of the predictive ability compared to the initial model and can enhance individual risk stratification . These results highlight the potential value of including genetic information in the usual models. Acknowledgments We are very grateful to Elsa Sousa who made all the administrative procedures and to Rita Freitas (CIDEHUS, Évora University, Portugal) who reviewed the paper for statistical analysis. Author contributions Conception and design of the research and Writing of the manuscript: Pereira A; Acquisition of data: Pereira A, Freitas AI, Sousa AC, Brehm A; Analysis and interpretation of the data and Statistical analysis: Pereira A, Freitas S, Henriques E, Rodrigues M; Critical revision of the manuscript for intellectual content: Pereira A, Mendonça MI, Borges S, Brehm A, Reis RP. Potential Conflict of Interest No potential conflict of interest relevant to this article was reported. Sources of Funding There were no external funding sources for this study. Study Association This article is part of the thesis of Doctoral submitted by Andreia Pereira, from Universidade Nova de Lisboa. Ethics approval and consent to participate This study was approved by the Ethics Committee of the SESARAM, EPE under the protocol number 50/2012. All the procedures in this study were in accordance with the 1975 Helsinki Declaration, updated in 2013. Informed consent was obtained from all participants included in the study. 58