title: A single nucleotide polymorphism within DUSP9 is associated with susceptibility to type 2 diabetes in a Japanese population.
abstract: OBJECTIVE
  The DUSP9 locus on chromosome X was identified as a susceptibility locus for type 2 diabetes in a meta-analysis of European genome-wide association studies (GWAS), and GWAS in South Asian populations identified 6 additional single nucleotide polymorphism (SNP) loci for type 2 diabetes. However, the association of these loci with type 2 diabetes have not been examined in the Japanese. We performed a replication study to investigate the association of these 7 susceptibility loci with type 2 diabetes in the Japanese population.
  
  
  METHODS
  We genotyped 11,319 Japanese participants (8,318 with type 2 diabetes and 3,001 controls) for each of the 7 SNPs-rs5945326 near DUSP9, rs3923113 near GRB14, rs16861329 in ST6GAL1, rs1802295 in VPS26A, rs7178572 in HMG20A, rs2028299 near AP3S2, and rs4812829 in HNF4A-and examined the association of each of these 7 SNPs with type 2 diabetes by using logistic regression analysis.
  
  
  RESULTS
  All SNPs had the same direction of effect (odds ratio [OR]>1.0) as in the original reports. One SNP, rs5945326 near DUSP9, was significantly associated with type 2 diabetes at a genome-wide significance level (p = 2.21×10(-8); OR 1.39, 95% confidence interval [CI]: 1.24-1.56). The 6 SNPs derived from South Asian GWAS were not significantly associated with type 2 diabetes in the Japanese population by themselves (p≥0.007). However, a genetic risk score constructed from 6 South Asian GWAS derived SNPs was significantly associated with Japanese type 2 diabetes (p = 8.69×10(-4), OR  = 1.06. 95% CI; 1.03-1.10).
  
  
  CONCLUSIONS
  These results indicate that the DUSP9 locus is a common susceptibility locus for type 2 diabetes across different ethnicities, and 6 loci identified in South Asian GWAS also have significant effect on susceptibility to Japanese type 2 diabetes.
authors.affiliation: Laboratory for Endocrinology and Metabolism, RIKEN Center for Genomic Medicine, Yokohama 230-0045, Japan.
authors.forename: Hisashi
authors.initials: H
authors.lastname: Fukuda
authors.forename: Minako
authors.initials: M
authors.lastname: Imamura
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Tanaka
authors.forename: Minoru
authors.initials: M
authors.lastname: Iwata
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Hirose
authors.forename: Kohei
authors.initials: K
authors.lastname: Kaku
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Maegawa
authors.forename: Hirotaka
authors.initials: H
authors.lastname: Watada
authors.forename: Kazuyuki
authors.initials: K
authors.lastname: Tobe
authors.forename: Atsunori
authors.initials: A
authors.lastname: Kashiwagi
authors.forename: Ryuzo
authors.initials: R
authors.lastname: Kawamori
authors.forename: Shiro
authors.initials: S
authors.lastname: Maeda
mesh_terms: D000368:Aged; D044466:Asian People; D016022:Case-Control Studies; D041321:Chromosomes, Human, X; D003924:Diabetes Mellitus, Type 2 / Q000453:epidemiology / Q000235:genetics*; D054637:Dual-Specificity Phosphatases / Q000235:genetics*; D005260:Female; D056426:Genetic Loci; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006801:Humans; D007564:Japan / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D054639:Mitogen-Activated Protein Kinase Phosphatases / Q000235:genetics*; D058889:Molecular Typing; D020641:Polymorphism, Single Nucleotide; D012306:Risk; D044465:White People
chemical_list: D054639:Mitogen-Activated Protein Kinase Phosphatases; C104821:DUSP9 protein, human; D054637:Dual-Specificity Phosphatases