Predictive performance of a genetic risk score using 11 susceptibility alleles for the incidence of Type 2 diabetes in a general Japanese population: a nested case-control study.

Abstract

AIMS:

To assess the predictive ability of a genetic risk score for the incidence of Type 2 diabetes in a general Japanese population.

METHODS:

This prospective case-control study, nested within a Japan Public Health Centre-based prospective study, included 466 participants with incident Type 2 diabetes over a 5-year period (cases) and 1361 control participants, as well as 1463 participants with existing diabetes and 1463 control participants. Eleven susceptibility single nucleotide polymorphisms, identified through genome-wide association studies and replicated in Japanese populations, were analysed.

RESULTS:

Most single nucleotide polymorphism loci showed directionally consistent associations with diabetes. From the combined samples, one single nucleotide polymorphism (rs2206734 at CDKAL1) reached a genome-wide significance level (odds ratio 1.28, 95% CI 1.18-1.40; P = 1.8 × 10-8 ). Three single nucleotide polymorphisms (rs2206734 in CDKAL1, rs2383208 in CDKN2A/B, and rs2237892 in KCNQ1) were nominally significantly associated with incident diabetes. Compared with the lowest quintile of the total number of risk alleles, the highest quintile had a higher odds of incident diabetes (odds ratio 2.34, 95% CI 1.59-3.46) after adjusting for conventional risk factors such as age, sex and BMI. The addition to the conventional risk factor-based model of a genetic risk score using the 11 single nucleotide polymorphisms significantly improved predictive performance; the c-statistic increased by 0.021, net reclassification improved by 6.2%, and integrated discrimination improved by 0.003.

CONCLUSIONS:

Our prospective findings suggest that the addition of a genetic risk score may provide modest but significant incremental predictive performance beyond that of the conventional risk factor-based model without biochemical markers.

• Authors: A Goto, M Noda, M Goto, K Yasuda, T Mizoue, T Yamaji, N Sawada, M Iwasaki, M Inoue, S Tsugane, JPHC Study Group
• Journal: Diabetic medicine : a journal of the British Diabetic Association (Diabet Med) Vol. 35 Issue 5 Pg. 602-611 (05 2018) ISSN: 1464-5491 [Electronic] England
• PMID: 29444352 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2018 Diabetes UK.

Chemical References

• C2CD4A protein, human
• CDKN2A protein, human
• CDKN2B protein, human
• Cyclin-Dependent Kinase Inhibitor p15
• Cyclin-Dependent Kinase Inhibitor p16
• Cyclin-Dependent Kinase Inhibitor p18
• HHEX protein, human
• Homeodomain Proteins
• IGFBP2 protein, human
• IRS1 protein, human
• Insulin Receptor Substrate Proteins
• Insulin-Like Growth Factor Binding Protein 2
• KCNQ1 Potassium Channel
• KCNQ1 protein, human
• Kir6.2 channel
• Nuclear Proteins
• PPAR gamma
• Potassium Channels, Inwardly Rectifying
• TCF7L2 protein, human
• Transcription Factor 7-Like 2 Protein
• Transcription Factors
• Alpha-Ketoglutarate-Dependent Dioxygenase FTO
• FTO protein, human
• tRNA Methyltransferases
• UBE2E2 protein, human
• Ubiquitin-Conjugating Enzymes
• CDKAL1 protein, human

Topics

• Adult
• Aged
• Alpha-Ketoglutarate-Dependent Dioxygenase FTO (genetics)
• Asian People (genetics)
• Case-Control Studies
• Cyclin-Dependent Kinase Inhibitor p15 (genetics)
• Cyclin-Dependent Kinase Inhibitor p16
• Cyclin-Dependent Kinase Inhibitor p18 (genetics)
• Diabetes Mellitus, Type 2 (epidemiology, genetics)
• Female
• Genetic Predisposition to Disease
• Homeodomain Proteins (genetics)
• Humans
• Incidence
• Insulin Receptor Substrate Proteins (genetics)
• Insulin-Like Growth Factor Binding Protein 2 (genetics)
• Japan (epidemiology)
• KCNQ1 Potassium Channel (genetics)
• Male
• Middle Aged
• Nuclear Proteins (genetics)
• PPAR gamma (genetics)
• Potassium Channels, Inwardly Rectifying (genetics)
• Prospective Studies
• Risk Assessment
• Risk Factors
• Transcription Factor 7-Like 2 Protein (genetics)
• Transcription Factors (genetics)
• Ubiquitin-Conjugating Enzymes (genetics)
• tRNA Methyltransferases (genetics)