title: Type 2 diabetes and polymorphisms on chromosome 9p21: a meta-analysis.
abstract: OBJECTIVE
  Genome-wide association studies found some variants on chromosome 9p21 associated with type 2 diabetes (T2D). We performed a meta-analysis to estimate strength, accuracy and feature of the association of polymorphisms in 9p21 with T2D.
  
  
  RESULTS
  Articles were retrieved screening electronic databases and cross references. Twenty-two publications were identified, for a total of 38,455 T2D patients and 60,516 controls. Twenty-one studies investigated the role of the SNP rs10811661; in some studies three additional SNPs (rs564398, rs10757278, rs1333040) were genotyped. Population attributable risk (PAR) was computed as: risk allele frequency∗(OR-1)/OR, using the per-allele odds ratio (OR). The risk allele (T) of rs10811661 was associated with T2D in most of the studies. In meta-analysis the overall per-allele OR was 1.24 (95% CI: 1.21-1.27; P < 10(-15)), with no difference according to ethnicity (P = 0.45), and low heterogeneity (P = 0.040) across studies partly explained by sample size. Modeling of inheritance suggested an additive effect of the T allele. PAR of T2D related to this polymorphism was 15% for Caucasians and 13% for Asians. The overall odds ratio for the T allele of the SNP rs564398 was 1.08 (95% CI: 1.05-1.12; PAR = 6%). The other SNPs showed negligible associations.
  
  
  CONCLUSIONS
  This meta-analysis provides accurate and comprehensive estimates of the association of some genetic variants at chromosome 9p21 and T2D. A relatively small but significant role of the T allele of the rs10811661 SNP in increasing by 21-27% the risk of T2D in an additive way was apparent.
authors.affiliation: Laboratorio di Epidemiologia Genetica ed Ambientale, Laboratori di Ricerca, Centro di Ricerche e Formazione ad Alta Tecnologia nelle Scienze Biomediche Giovanni Paolo II, Università Cattolica del Sacro Cuore, Campobasso, Italy.
authors.forename: D
authors.initials: D
authors.lastname: Cugino
authors.forename: F
authors.initials: F
authors.lastname: Gianfagna
authors.forename: I
authors.initials: I
authors.lastname: Santimone
authors.forename: G
authors.initials: G
authors.lastname: de Gaetano
authors.forename: M B
authors.initials: MB
authors.lastname: Donati
authors.forename: L
authors.initials: L
authors.lastname: Iacoviello
authors.forename: A
authors.initials: A
authors.lastname: Di Castelnuovo
mesh_terms: D002899:Chromosomes, Human, Pair 9; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics*; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D040941:Heredity; D006801:Humans; D015810:Linkage Disequilibrium; D016017:Odds Ratio; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D018570:Risk Assessment; D012307:Risk Factors