title: Cumulative effect and predictive value of genetic variants associated with type 2 diabetes in Han Chinese: a case-control study.
abstract: BACKGROUND
  Genome-wide association studies (GWAS) have identified dozens of single nucleotide polymorphisms (SNPs) associated with type 2 diabetes risk. We have previously confirmed the associations of genetic variants in HHEX, CDKAL1, VEGFA and FTO with type 2 diabetes in Han Chinese. However, the cumulative effect and predictive value of these GWAS identified SNPs on the risk of type 2 diabetes in Han Chinese are largely unknown.
  
  
  RESULTS
  We conducted a two-stage case-control study consisting of 2,925 cases and 3,281 controls to examine the association of 30 SNPs identified by GWAS with type 2 diabetes in Han Chinese. Significant associations were found for proxy SNPs at KCNQ1 [odds ratio (OR) = 1.41, P = 9.91 × 10-16 for rs2237897], CDKN2A/CDKN2B (OR = 1.30, P = 1.34 × 10-10 for rs10811661), CENTD2 (OR = 1.28, P = 9.88 × 10-4 for rs1552224) and SLC30A8 (OR = 1.19, P = 1.43 × 10-5 for rs13266634). We further evaluated the cumulative effect on type 2 diabetes of these 4 SNPs, in combination with 5 SNPs at HHEX, CDKAL1, VEGFA and FTO reported previously. Individuals carrying 12 or more risk alleles had a nearly 4-fold increased risk for developing type 2 diabetes compared with those carrying less than 6 risk alleles [adjusted OR = 3.68, 95% confidence interval (CI): 2.76-4.91]. Adding the genetic factors to clinical factors slightly improved the prediction of type 2 diabetes, with the area under the receiver operating characteristic curve increasing from 0.76 to 0.78. However, the difference was statistically significant (P < 0.0001).
  
  
  CONCLUSIONS
  We confirmed associations of SNPs in KCNQ1, CDKN2A/CDKN2B, CENTD2 and SLC30A8 with type 2 diabetes in Han Chinese. The utilization of genetic information may improve the accuracy of risk prediction in combination with clinical characteristics for type 2 diabetes.
authors.affiliation: Department of Chronic Non-communicable Disease Control, Wuxi Center for Disease Control and Prevention, Wuxi 214023, China.
authors.forename: Yun
authors.initials: Y
authors.lastname: Qian
authors.affiliation: Department of Epidemiology and Biostatistics, School of Public Health, Nanjing Medical University, Nanjing 210029, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Lu
authors.affiliation: Department of Chronic Non-communicable Disease Control, Wuxi Center for Disease Control and Prevention, Wuxi 214023, China.
authors.forename: Meihua
authors.initials: M
authors.lastname: Dong
authors.affiliation: Department of Chronic Non-communicable Disease Control, Wuxi Center for Disease Control and Prevention, Wuxi 214023, China.
authors.forename: Yudi
authors.initials: Y
authors.lastname: Lin
authors.affiliation: Department of Epidemiology and Biostatistics, School of Public Health, Nanjing Medical University, Nanjing 210029, China.
authors.forename: Huizhang
authors.initials: H
authors.lastname: Li
authors.affiliation: Department of Epidemiology and Biostatistics, School of Public Health, Nanjing Medical University, Nanjing 210029, China.
authors.forename: Juncheng
authors.initials: J
authors.lastname: Dai
authors.affiliation: Department of Epidemiology and Biostatistics, School of Public Health, Nanjing Medical University, Nanjing 210029, China.
authors.forename: Guangfu
authors.initials: G
authors.lastname: Jin
authors.affiliation: Department of Epidemiology and Biostatistics, School of Public Health, Nanjing Medical University, Nanjing 210029, China.
authors.forename: Zhibin
authors.initials: Z
authors.lastname: Hu
authors.affiliation: Department of Epidemiology and Biostatistics, School of Public Health, Nanjing Medical University, Nanjing 210029, China.
authors.forename: Hongbing
authors.initials: H
authors.lastname: Shen
mesh_terms: D000483:Alleles; D044466:Asian People / Q000235:genetics*; D016022:Case-Control Studies; D003430:Cross-Sectional Studies; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011237:Predictive Value of Tests; D012306:Risk