Construction of a prediction model for type 2 diabetes mellitus in the Japanese population based on 11 genes with strong evidence of the association.
Prediction of the disease status is one of the most important objectives of genetic studies. To select the genes with strong evidence of the association with type 2 diabetes mellitus, we validated the associations of the seven candidate loci extracted in our earlier study by genotyping the samples in two independent sample panels. However, except for KCNQ1, the association of none of the remaining seven loci was replicated. We then selected 11 genes, KCNQ1, TCF7L2, CDKAL1, CDKN2A/B, IGF2BP2, SLC30A8, HHEX, GCKR, HNF1B, KCNJ11 and PPARG, whose associations with diabetes have already been reported and replicated either in the literature or in this study in the Japanese population. As no evidence of the gene-gene interaction for any pair of the 11 loci was shown, we constructed a prediction model for the disease using the logistic regression analysis by incorporating the number of the risk alleles for the 11 genes, as well as age, sex and body mass index as independent variables. Cumulative risk assessment showed that the addition of one risk allele resulted in an average increase in the odds for the disease of 1.29 (95% CI=1.25-1.33, P=5.4 x 10(-53)). The area under the receiver operating characteristic curve, an estimate of the power of the prediction model, was 0.72, thereby indicating that our prediction model for type 2 diabetes may not be so useful but has some value. Incorporation of data from additional risk loci is most likely to increase the predictive power.
Miyake
Kazuaki
K
Division of Diabetes, Metabolism and Endocrinology, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe, Japan.
Yang
Woosung
W
Hara
Kazuo
K
Yasuda
Kazuki
K
Horikawa
Yukio
Y
Osawa
Haruhiko
H
Furuta
Hiroto
H
Ng
Maggie C Y
MC
Hirota
Yushi
Y
Mori
Hiroyuki
H
Ido
Keisuke
K
Yamagata
Kazuya
K
Hinokio
Yoshinori
Y
Oka
Yoshitomo
Y
Iwasaki
Naoko
N
Iwamoto
Yasuhiko
Y
Yamada
Yuichiro
Y
Seino
Yutaka
Y
Maegawa
Hiroshi
H
Kashiwagi
Atsunori
A
Wang
He-Yao
HY
Tanahashi
Toshihito
T
Nakamura
Naoto
N
Takeda
Jun
J
Maeda
Eiichi
E
Yamamoto
Ken
K
Tokunaga
Katsushi
K
Ma
Ronald C W
RC
So
Wing-Yee
WY
Chan
Juliana C N
JC
Kamatani
Naoyuki
N
Makino
Hideichi
H
Nanjo
Kishio
K
Kadowaki
Takashi
T
Kasuga
Masato
M
D000483:Alleles; D044466:Asian People / Q000235:genetics*; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D005820:Genetic Testing; D055106:Genome-Wide Association Study; D006801:Humans; D007564:Japan; D008957:Models, Genetic; D016017:Odds Ratio; D012372:ROC Curve; D015203:Reproducibility of Results; D018570:Risk Assessment