Prediction of type 2 diabetes using genome-wide polygenic risk score and metabolic profiles: A machine learning analysis of population-based 10-year prospective cohort study

eBioMedicineeBioMedicineVolume 86, December 2022, 104383Journal home page for eBioMedicineAuthor links open overlay panelSummaryBackground

Previous work on predicting type 2 diabetes by integrating clinical and genetic factors has mostly focused on the Western population. In this study, we use genome-wide polygenic risk score (gPRS) and serum metabolite data for type 2 diabetes risk prediction in the Asian population.

Methods

Data of 1425 participants from the Korean Genome and Epidemiology Study (KoGES) Ansan-Ansung cohort were used in this study. For gPRS analysis, genotypic and clinical information from KoGES health examinee (n = 58,701) and KoGES cardiovascular disease association (n = 8105) sub-cohorts were included. Linkage disequilibrium analysis identified 239,062 genetic variants that were used to determine the gPRS, while the metabolites were selected using the Boruta algorithm. We used bootstrapped cross-validation to evaluate logistic regression and random forest (RF)-based machine learning models. Finally, associations of gPRS and selected metabolites with the values of homeostatic model assessment of beta-cell function (HOMA-B) and insulin resistance (HOMA-IR) were further estimated.

Findings

During the follow-up period (8.3 ± 2.8 years), 331 participants (23.2%) were diagnosed with type 2 diabetes. The areas under the curves of the RF-based models were 0.844, 0.876, and 0.883 for the model using only demographic and clinical factors, model including the gPRS, and model with both gPRS and metabolites, respectively. Incorporation of additional parameters in the latter two models improved the classification by 11.7% and 4.2% respectively. While gPRS was significantly associated with HOMA-B value, most metabolites had a significant association with HOMA-IR value.

Interpretation

Incorporating both gPRS and metabolite data led to enhanced type 2 diabetes risk prediction by capturing distinct etiologies of type 2 diabetes development. An RF-based model using clinical factors, gPRS, and metabolites predicted type 2 diabetes risk more accurately than the logistic regression-based model.

Funding

This work was supported by the National Research Foundation of Korea (NRF) grant funded by the Korean government (MEST) (No. 2019M3E5D1A02070863 and 2022R1C1C1005458). This work was also supported by the 2020 Research Fund (1.200098.01) of UNIST (Ulsan National Institute of Science & Technology)

Keywords

Type 2 diabetes

Genome-wide polygenic risk score

Machine learning

Serum metabolites

KoGES

East Asian

AbbreviationsgPRS

genome-wide polygenic risk score

KoGES

Korean genome and epidemiology study

HOMA-B

homeostatic model assessment of beta-cell function

HOMA-IR

homeostatic model assessment of insulin resistance

BCAA

branched-chain amino acids

FOS

Framingham offspring study

TAC

total alcohol consumption

HDL

high-density lipoprotein

HEXA

KoGES health examinee study

CAVAS

KoGES cardiovascular disease association study

GWAS

genome-wide association study

SNP

single nucleotide polymorphism

MDI

mean decrease impurity

AUC

area under receiver operating characteristic curve

© 2022 The Author(s). Published by Elsevier B.V.

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