title: Genome-wide association study of type 2 diabetes in a sample from Mexico City and a meta-analysis of a Mexican-American sample from Starr County, Texas.
abstract: OBJECTIVE
  We report a genome-wide association study of type 2 diabetes in an admixed sample from Mexico City and describe the results of a meta-analysis of this study and another genome-wide scan in a Mexican-American sample from Starr County, TX, USA. The top signals observed in this meta-analysis were followed up in the Diabetes Genetics Replication and Meta-analysis Consortium (DIAGRAM) and DIAGRAM+ datasets.
  
  
  METHODS
  We analysed 967 cases and 343 normoglycaemic controls. The samples were genotyped with the Affymetrix Genome-wide Human SNP array 5.0. Associations of genotyped and imputed markers with type 2 diabetes were tested using a missing data likelihood score test. A fixed-effects meta-analysis including 1,804 cases and 780 normoglycaemic controls was carried out by weighting the effect estimates by their inverse variances.
  
  
  RESULTS
  In the meta-analysis of the two Hispanic studies, markers showing suggestive associations (p < 10(-5)) were identified in two known diabetes genes, HNF1A and KCNQ1, as well as in several additional regions. Meta-analysis of the two Hispanic studies and the recent DIAGRAM+ dataset identified genome-wide significant signals (p < 5 × 10(-8)) within or near the genes HNF1A and CDKN2A/CDKN2B, as well as suggestive associations in three additional regions, IGF2BP2, KCNQ1 and the previously unreported C14orf70.
  
  
  CONCLUSIONS
  We observed numerous regions with suggestive associations with type 2 diabetes. Some of these signals correspond to regions described in previous studies. However, many of these regions could not be replicated in the DIAGRAM datasets. It is critical to carry out additional studies in Hispanic and American Indian populations, which have a high prevalence of type 2 diabetes.
authors.affiliation: Department of Anthropology, University of Toronto at Mississauga, 3359 Mississauga Road North, Mississauga, ON, Canada, L5L 1C6. esteban.parra@utoronto.ca
authors.forename: E J
authors.initials: EJ
authors.lastname: Parra
authors.forename: J E
authors.initials: JE
authors.lastname: Below
authors.forename: S
authors.initials: S
authors.lastname: Krithika
authors.forename: A
authors.initials: A
authors.lastname: Valladares
authors.forename: J L
authors.initials: JL
authors.lastname: Barta
authors.forename: N J
authors.initials: NJ
authors.lastname: Cox
authors.forename: C L
authors.initials: CL
authors.lastname: Hanis
authors.forename: N
authors.initials: N
authors.lastname: Wacher
authors.forename: J
authors.initials: J
authors.lastname: Garcia-Mena
authors.forename: P
authors.initials: P
authors.lastname: Hu
authors.forename: M D
authors.initials: MD
authors.lastname: Shriver
authors.forename: J
authors.initials: J
authors.lastname: Kumate
authors.forename: P M
authors.initials: PM
authors.lastname: McKeigue
authors.forename: J
authors.initials: J
authors.lastname: Escobedo
authors.forename: M
authors.initials: M
authors.lastname: Cruz
mesh_terms: D000328:Adult; D000368:Aged; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics*; D005260:Female; D055106:Genome-Wide Association Study / Q000379:methods*; D005838:Genotype; D006630:Hispanic or Latino / Q000235:genetics; D006801:Humans; D008297:Male; D017058:Mexican Americans / Q000235:genetics; D008800:Mexico; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D013781:Texas; D055815:Young Adult