title: Construction of a prediction model for type 2 diabetes mellitus in the Japanese population based on 11 genes with strong evidence of the association.
abstract: 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.
authors.affiliation: Division of Diabetes, Metabolism and Endocrinology, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe, Japan.
authors.forename: Kazuaki
authors.initials: K
authors.lastname: Miyake
authors.forename: Woosung
authors.initials: W
authors.lastname: Yang
authors.forename: Kazuo
authors.initials: K
authors.lastname: Hara
authors.forename: Kazuki
authors.initials: K
authors.lastname: Yasuda
authors.forename: Yukio
authors.initials: Y
authors.lastname: Horikawa
authors.forename: Haruhiko
authors.initials: H
authors.lastname: Osawa
authors.forename: Hiroto
authors.initials: H
authors.lastname: Furuta
authors.forename: Maggie C Y
authors.initials: MC
authors.lastname: Ng
authors.forename: Yushi
authors.initials: Y
authors.lastname: Hirota
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Mori
authors.forename: Keisuke
authors.initials: K
authors.lastname: Ido
authors.forename: Kazuya
authors.initials: K
authors.lastname: Yamagata
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Hinokio
authors.forename: Yoshitomo
authors.initials: Y
authors.lastname: Oka
authors.forename: Naoko
authors.initials: N
authors.lastname: Iwasaki
authors.forename: Yasuhiko
authors.initials: Y
authors.lastname: Iwamoto
authors.forename: Yuichiro
authors.initials: Y
authors.lastname: Yamada
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Seino
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Maegawa
authors.forename: Atsunori
authors.initials: A
authors.lastname: Kashiwagi
authors.forename: He-Yao
authors.initials: HY
authors.lastname: Wang
authors.forename: Toshihito
authors.initials: T
authors.lastname: Tanahashi
authors.forename: Naoto
authors.initials: N
authors.lastname: Nakamura
authors.forename: Jun
authors.initials: J
authors.lastname: Takeda
authors.forename: Eiichi
authors.initials: E
authors.lastname: Maeda
authors.forename: Ken
authors.initials: K
authors.lastname: Yamamoto
authors.forename: Katsushi
authors.initials: K
authors.lastname: Tokunaga
authors.forename: Ronald C W
authors.initials: RC
authors.lastname: Ma
authors.forename: Wing-Yee
authors.initials: WY
authors.lastname: So
authors.forename: Juliana C N
authors.initials: JC
authors.lastname: Chan
authors.forename: Naoyuki
authors.initials: N
authors.lastname: Kamatani
authors.forename: Hideichi
authors.initials: H
authors.lastname: Makino
authors.forename: Kishio
authors.initials: K
authors.lastname: Nanjo
authors.forename: Takashi
authors.initials: T
authors.lastname: Kadowaki
authors.forename: Masato
authors.initials: M
authors.lastname: Kasuga
mesh_terms: 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