title: Genetic information and the prediction of incident type 2 diabetes in a high-risk multiethnic population: the EpiDREAM genetic study.
abstract: OBJECTIVE
  To determine if 16 single nucleotide polymorphisms (SNPs) associated with type 2 diabetes (T2DM) in Europeans are also associated with T2DM in South Asians and Latinos and if they can add to the prediction of incident T2DM in a high-risk population.
  
  
  METHODS
  In the EpiDREAM prospective cohort study, physical measures, questionnaires, and blood samples were collected from 25,063 individuals at risk for dysglycemia. Sixteen SNPs that have been robustly associated with T2DM in Europeans were genotyped. Among 15,466 European, South Asian, and Latino subjects, we examined the association of these 16 SNPs alone and combined in a gene score with incident cases of T2DM (n = 1,016) that developed during 3.3 years of follow-up.
  
  
  RESULTS
  Nine of the 16 SNPs were significantly associated with T2DM, and their direction of effect was consistent across the three ethnic groups. The gene score was significantly higher among subjects who developed incident T2DM (cases vs. noncases: 16.47 [2.50] vs. 15.99 [2.56]; P = 0.00001). The gene score remained an independent predictor of incident T2DM, with an odds ratio of 1.08 (95% CI 1.05-1.11) per additional risk allele after adjustment for T2DM risk factors. The gene score in those with no family history of T2DM was 16.02, whereas it was 16.19 in those with one parent with T2DM and it was 16.32 in those with two parents with T2DM (P trend = 0.0004). The C statistic of T2DM risk factors was 0.708 (0.691-0.725) and increased only marginally to 0.714 (0.698-0.731) with the addition of the gene score (P for C statistic change = 0.0052).
  
  
  CONCLUSIONS
  T2DM genetic associations are generally consistent across ethnic groups, and a gene score only adds marginal information to clinical factors for T2DM prediction.
authors.affiliation: Population Health Research Institute, McMaster University and Hamilton Health Sciences, Hamilton General Hospital, Hamilton, Ontario, Canada. anands@mcmaster.ca
authors.forename: Sonia S
authors.initials: SS
authors.lastname: Anand
authors.forename: David
authors.initials: D
authors.lastname: Meyre
authors.forename: Guillaume
authors.initials: G
authors.lastname: Pare
authors.forename: Swneke D
authors.initials: SD
authors.lastname: Bailey
authors.forename: Changchun
authors.initials: C
authors.lastname: Xie
authors.forename: Xiaohe
authors.initials: X
authors.lastname: Zhang
authors.forename: Alexandre
authors.initials: A
authors.lastname: Montpetit
authors.forename: Dipika
authors.initials: D
authors.lastname: Desai
authors.forename: Jackie
authors.initials: J
authors.lastname: Bosch
authors.forename: Viswanathan
authors.initials: V
authors.lastname: Mohan
authors.forename: Rafael
authors.initials: R
authors.lastname: Diaz
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: McQueen
authors.forename: Heather J
authors.initials: HJ
authors.lastname: Cordell
authors.forename: Bernard
authors.initials: B
authors.lastname: Keavney
authors.forename: Salim
authors.initials: S
authors.lastname: Yusuf
authors.forename: Daniel
authors.initials: D
authors.lastname: Gaudet
authors.forename: Hertzel
authors.initials: H
authors.lastname: Gerstein
authors.forename: James C
authors.initials: JC
authors.lastname: Engert
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics*; D005838:Genotype; D006801:Humans; D008875:Middle Aged; D015999:Multivariate Analysis; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D044465:White People / Q000235:genetics; D055815:Young Adult