title: Screening of 134 single nucleotide polymorphisms (SNPs) previously associated with type 2 diabetes replicates association with 12 SNPs in nine genes.
abstract: More than 120 published reports have described associations between single nucleotide polymorphisms (SNPs) and type 2 diabetes. However, multiple studies of the same variant have often been discordant. From a literature search, we identified previously reported type 2 diabetes-associated SNPs. We initially genotyped 134 SNPs on 786 index case subjects from type 2 diabetes families and 617 control subjects with normal glucose tolerance from Finland and excluded from analysis 20 SNPs in strong linkage disequilibrium (r(2) > 0.8) with another typed SNP. Of the 114 SNPs examined, we followed up the 20 most significant SNPs (P < 0.10) on an additional 384 case subjects and 366 control subjects from a population-based study in Finland. In the combined data, we replicated association (P < 0.05) for 12 SNPs: PPARG Pro12Ala and His447, KCNJ11 Glu23Lys and rs5210, TNF -857, SLC2A2 Ile110Thr, HNF1A/TCF1 rs2701175 and GE117881_360, PCK1 -232, NEUROD1 Thr45Ala, IL6 -598, and ENPP1 Lys121Gln. The replication of 12 SNPs of 114 tested was significantly greater than expected by chance under the null hypothesis of no association (P = 0.012). We observed that SNPs from genes that had three or more previous reports of association were significantly more likely to be replicated in our sample (P = 0.03), although we also replicated 4 of 58 SNPs from genes that had only one previous report of association.
authors.affiliation: Department of Biostatistics, Center for Statistical Genetics, University of Michigan, Ann Arbor 48109-2029, USA.
authors.forename: Cristen J
authors.initials: CJ
authors.lastname: Willer
authors.forename: Lori L
authors.initials: LL
authors.lastname: Bonnycastle
authors.forename: Karen N
authors.initials: KN
authors.lastname: Conneely
authors.forename: William L
authors.initials: WL
authors.lastname: Duren
authors.forename: Anne U
authors.initials: AU
authors.lastname: Jackson
authors.forename: Laura J
authors.initials: LJ
authors.lastname: Scott
authors.forename: Narisu
authors.initials: N
authors.lastname: Narisu
authors.forename: Peter S
authors.initials: PS
authors.lastname: Chines
authors.forename: Andrew
authors.initials: A
authors.lastname: Skol
authors.forename: Heather M
authors.initials: HM
authors.lastname: Stringham
authors.forename: John
authors.initials: J
authors.lastname: Petrie
authors.forename: Michael R
authors.initials: MR
authors.lastname: Erdos
authors.forename: Amy J
authors.initials: AJ
authors.lastname: Swift
authors.forename: Sareena T
authors.initials: ST
authors.lastname: Enloe
authors.forename: Andrew G
authors.initials: AG
authors.lastname: Sprau
authors.forename: Eboni
authors.initials: E
authors.lastname: Smith
authors.forename: Maurine
authors.initials: M
authors.lastname: Tong
authors.forename: Kimberly F
authors.initials: KF
authors.lastname: Doheny
authors.forename: Elizabeth W
authors.initials: EW
authors.lastname: Pugh
authors.forename: Richard M
authors.initials: RM
authors.lastname: Watanabe
authors.forename: Thomas A
authors.initials: TA
authors.lastname: Buchanan
authors.forename: Timo T
authors.initials: TT
authors.lastname: Valle
authors.forename: Richard N
authors.initials: RN
authors.lastname: Bergman
authors.forename: Jaakko
authors.initials: J
authors.lastname: Tuomilehto
authors.forename: Karen L
authors.initials: KL
authors.lastname: Mohlke
authors.forename: Francis S
authors.initials: FS
authors.lastname: Collins
authors.forename: Michael
authors.initials: M
authors.lastname: Boehnke
mesh_terms: D000368:Aged; D001786:Blood Glucose / Q000032:analysis; D015992:Body Mass Index; D002874:Chromosome Mapping; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics*; D005215:Fasting; D005260:Female; D005820:Genetic Testing; D006801:Humans; D007223:Infant; D007328:Insulin / Q000097:blood; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide
chemical_list: D001786:Blood Glucose; D007328:Insulin