Screening of 134 single nucleotide polymorphisms (SNPs) previously associated with type 2 diabetes replicates association with 12 SNPs in nine genes.
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.
Willer
Cristen J
CJ
Department of Biostatistics, Center for Statistical Genetics, University of Michigan, Ann Arbor 48109-2029, USA.
Bonnycastle
Lori L
LL
Conneely
Karen N
KN
Duren
William L
WL
Jackson
Anne U
AU
Scott
Laura J
LJ
Narisu
Narisu
N
Chines
Peter S
PS
Skol
Andrew
A
Stringham
Heather M
HM
Petrie
John
J
Erdos
Michael R
MR
Swift
Amy J
AJ
Enloe
Sareena T
ST
Sprau
Andrew G
AG
Smith
Eboni
E
Tong
Maurine
M
Doheny
Kimberly F
KF
Pugh
Elizabeth W
EW
Watanabe
Richard M
RM
Buchanan
Thomas A
TA
Valle
Timo T
TT
Bergman
Richard N
RN
Tuomilehto
Jaakko
J
Mohlke
Karen L
KL
Collins
Francis S
FS
Boehnke
Michael
M
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
D001786:Blood Glucose; D007328:Insulin