title: Utility of genetic and non-genetic risk factors in predicting coronary heart disease in Singaporean Chinese.
abstract: Background Although numerous phenotype based equations for predicting risk of 'hard' coronary heart disease are available, data on the utility of genetic information for such risk prediction is lacking in Chinese populations. Design Case-control study nested within the Singapore Chinese Health Study. Methods A total of 1306 subjects comprising 836 men (267 incident cases and 569 controls) and 470 women (128 incident cases and 342 controls) were included. A Genetic Risk Score comprising 156 single nucleotide polymorphisms that have been robustly associated with coronary heart disease or its risk factors ( p < 5 × 10-8) in at least two independent cohorts of genome-wide association studies was built. For each gender, three base models were used: recalibrated Adult Treatment Panel III (ATPIII) Model (M1); ATP III model fitted using Singapore Chinese Health Study data (M2) and M3: M2+ C-reactive protein + creatinine. Results The Genetic Risk Score was significantly associated with incident 'hard' coronary heart disease ( p for men: 1.70 × 10-10-1.73 × 10-9; p for women: 0.001). The inclusion of the Genetic Risk Score in the prediction models improved discrimination in both genders (c-statistics: 0.706-0.722 vs. 0.663-0.695 from base models for men; 0.788-0.790 vs. 0.765-0.773 for women). In addition, the inclusion of the Genetic Risk Score also improved risk classification with a net gain of cases being reclassified to higher risk categories (men: 12.4%-16.5%; women: 10.2% (M3)), while not significantly reducing the classification accuracy in controls. Conclusions The Genetic Risk Score is an independent predictor for incident 'hard' coronary heart disease in our ethnic Chinese population. Inclusion of genetic factors into coronary heart disease prediction models could significantly improve risk prediction performance.
authors: 1 Department of Paediatrics, Yong Loo Lin School of Medicine, National University of Singapore.|2 Khoo Teck Puat - National University Children's Medical Institute, National University Health System.
authors: Xuling
authors: X
authors: Chang
authors: 3 Department of Mathematics and Statistics, La Trobe University, Australia.|4 Saw Swee Hock School of Public Health, National University of Singapore and National University Health System.
authors: Agus
authors: A
authors: Salim
authors: 5 Genome Institute of Singapore, Agency for Science, Technology and Research, Singapore.
authors: Rajkumar
authors: R
authors: Dorajoo
authors: 1 Department of Paediatrics, Yong Loo Lin School of Medicine, National University of Singapore.|2 Khoo Teck Puat - National University Children's Medical Institute, National University Health System.
authors: Yi
authors: Y
authors: Han
authors: 5 Genome Institute of Singapore, Agency for Science, Technology and Research, Singapore.|6 Singapore Eye Research Institute, Singapore National Eye Center, Singapore.|7 Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
authors: Chiea-Chuen
authors: CC
authors: Khor
authors: 4 Saw Swee Hock School of Public Health, National University of Singapore and National University Health System.
authors: Rob M
authors: RM
authors: van Dam
authors: 8 Department of Epidemiology, Graduate School of Public Health; and University of Pittsburgh Cancer Institute, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
authors: Jian-Min
authors: JM
authors: Yuan
authors: 4 Saw Swee Hock School of Public Health, National University of Singapore and National University Health System.|9 Duke-NUS Medical School Singapore, Singapore.
authors: Woon-Puay
authors: WP
authors: Koh
authors: 4 Saw Swee Hock School of Public Health, National University of Singapore and National University Health System.|5 Genome Institute of Singapore, Agency for Science, Technology and Research, Singapore.|10 Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
authors: Jianjun
authors: J
authors: Liu
authors: 1 Department of Paediatrics, Yong Loo Lin School of Medicine, National University of Singapore.|2 Khoo Teck Puat - National University Children's Medical Institute, National University Health System.
authors: Daniel Yt
authors: DY
authors: Goh
authors: 4 Saw Swee Hock School of Public Health, National University of Singapore and National University Health System.
authors: Xu
authors: X
authors: Wang
authors: 4 Saw Swee Hock School of Public Health, National University of Singapore and National University Health System.|5 Genome Institute of Singapore, Agency for Science, Technology and Research, Singapore.|6 Singapore Eye Research Institute, Singapore National Eye Center, Singapore.|11 Life Sciences Institute, National University of Singapore, Singapore.|12 NUS Graduate School for Integrative Science and Engineering, National University of Singapore, Singapore.|13 Department of Statistics and Applied Probability, National University of Singapore, Singapore.
authors: Yik-Ying
authors: YY
authors: Teo
authors: 14 School of Public Health and Community Medicine, Hebrew University of Jerusalem.
authors: Yechiel
authors: Y
authors: Friedlander
authors: 1 Department of Paediatrics, Yong Loo Lin School of Medicine, National University of Singapore.|2 Khoo Teck Puat - National University Children's Medical Institute, National University Health System.
authors: Chew-Kiat
authors: CK
authors: Heng
mesh_terms: D000368:Aged; D044466:Asian People / Q000235:genetics*; D015415:Biomarkers / Q000097:blood; D002097:C-Reactive Protein / Q000032:analysis; D016022:Case-Control Studies; D002681:China / Q000208:ethnology; D003327:Coronary Disease / Q000097:blood / Q000175:diagnosis* / Q000208:ethnology / Q000235:genetics*; D003404:Creatinine / Q000097:blood; D005260:Female; D020022:Genetic Predisposition to Disease; D006306:Health Surveys; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D011379:Prognosis; D018570:Risk Assessment; D012307:Risk Factors; D012846:Singapore / Q000453:epidemiology
chemical_list: D015415:Biomarkers; D002097:C-Reactive Protein; D003404:Creatinine
keywords: Adult Treatment Panel III; Risk prediction; coronary heart disease; genetic factors