title: Common variants in maturity-onset diabetes of the young genes contribute to risk of type 2 diabetes in Finns.
abstract: Prior reports have suggested that variants in the genes for maturity-onset diabetes of the young (MODY) may confer susceptibility to type 2 diabetes, but results have been conflicting and coverage of the MODY genes has been incomplete. To complement our previous studies of HNF4A, we examined the other five known MODY genes for association with type 2 diabetes in Finnish individuals. For each of the five genes, we selected 1) nonredundant single nucleotide polymorphisms (SNPs) (r(2)< 0.8 with other SNPs) from the HapMap database or another linkage disequilibrium map, 2) SNPs with previously reported type 2 diabetes association, and 3) nonsynonymous coding SNPs. We tested 128 SNPs for association with type 2 diabetes in 786 index cases from type 2 diabetic families and 619 normal glucose-tolerant control subjects. We followed up 35 of the most significant SNPs by genotyping them on another 384 case subjects and 366 control subjects from Finland. We also supplemented our previous HNF4A results by genotyping 12 SNPs on additional Finnish samples. After correcting for testing multiple correlated SNPs within a gene, we find evidence of type 2 diabetes association with SNPs in five of the six known MODY genes: GCK, HNF1A, HNF1B, NEUROD1, and HNF4A. Our data suggest that common variants in several MODY genes play a modest role in type 2 diabetes susceptibility.
authors.affiliation: Genome Technology Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892-2152, USA.
authors.forename: Lori L
authors.initials: LL
authors.lastname: Bonnycastle
authors.forename: Cristen J
authors.initials: CJ
authors.lastname: Willer
authors.forename: Karen N
authors.initials: KN
authors.lastname: Conneely
authors.forename: Anne U
authors.initials: AU
authors.lastname: Jackson
authors.forename: Cecily P
authors.initials: CP
authors.lastname: Burrill
authors.forename: Richard M
authors.initials: RM
authors.lastname: Watanabe
authors.forename: Peter S
authors.initials: PS
authors.lastname: Chines
authors.forename: Narisu
authors.initials: N
authors.lastname: Narisu
authors.forename: Laura J
authors.initials: LJ
authors.lastname: Scott
authors.forename: Sareena T
authors.initials: ST
authors.lastname: Enloe
authors.forename: Amy J
authors.initials: AJ
authors.lastname: Swift
authors.forename: William L
authors.initials: WL
authors.lastname: Duren
authors.forename: Heather M
authors.initials: HM
authors.lastname: Stringham
authors.forename: Michael R
authors.initials: MR
authors.lastname: Erdos
authors.forename: Nancy L
authors.initials: NL
authors.lastname: Riebow
authors.forename: Thomas A
authors.initials: TA
authors.lastname: Buchanan
authors.forename: Timo T
authors.initials: TT
authors.lastname: Valle
authors.forename: Jaakko
authors.initials: J
authors.lastname: Tuomilehto
authors.forename: Richard N
authors.initials: RN
authors.lastname: Bergman
authors.forename: Karen L
authors.initials: KL
authors.lastname: Mohlke
authors.forename: Michael
authors.initials: M
authors.lastname: Boehnke
authors.forename: Francis S
authors.initials: FS
authors.lastname: Collins
mesh_terms: D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics*; D003924:Diabetes Mellitus, Type 2 / Q000209:etiology / Q000235:genetics*; D005260:Female; D005387:Finland; D005941:Glucokinase / Q000235:genetics; D051538:Hepatocyte Nuclear Factor 1-alpha / Q000235:genetics*; D051539:Hepatocyte Nuclear Factor 1-beta / Q000235:genetics*; D051557:Hepatocyte Nuclear Factor 4 / Q000235:genetics*; D018398:Homeodomain Proteins / Q000235:genetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D015534:Trans-Activators / Q000235:genetics
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D005941:Glucokinase; D051538:Hepatocyte Nuclear Factor 1-alpha; D051539:Hepatocyte Nuclear Factor 1-beta; D051557:Hepatocyte Nuclear Factor 4; D018398:Homeodomain Proteins; D015534:Trans-Activators; C496487:HNF1A protein, human; C496495:HNF1B protein, human; C496592:HNF4A protein, human; C093970:NEUROD1 protein, human; C084010:pancreatic and duodenal homeobox 1 protein