# Real-World Utility of GWAS-Based Diabetes Mellitus Panel Testing

## TL;DR

This study shows that a genetic test can predict diabetes risk in healthy people and suggests that smoking can increase risk in those already genetically predisposed.

## Contribution

The study demonstrates the clinical utility of a PRS-based diabetes panel and identifies gene-smoking interactions in risk prediction.

## Key findings

- The very high-risk group had significantly higher fasting blood glucose and HbA1c levels and a 4.5-fold increased risk of developing diabetes.
- Smoking increased diabetes risk by 25% in the very high-risk genetic group.
- HHEX variants in the high-risk group showed the greatest susceptibility, especially among current smokers.

## Abstract

This study evaluated the clinical utility of a polygenic risk score (PRS)-based multigene panel test for predicting diabetes mellitus (DM) in a healthy population. A total of 302 individuals underwent genetic testing using the HelloGene™ DM panel, which includes four DM-related single nucleotide polymorphisms (CDKAL1, HHEX, KCNQ1, and TCF7L2). PRS values were calculated using an algorithm developed from the Korean Genome and Epidemiology Study (KoGES; n = 39,605), and participants were classified into four genetic risk groups (low, moderate, high, and very high). Fasting blood glucose, glycated hemoglobin (HbA1c), and body mass index were assessed at baseline and after at least three years of follow-up, and lifestyle factors including smoking, alcohol consumption, and exercise status were recorded. No significant differences in age, sex, or lifestyle habits were observed among PRS groups. The very high-risk group showed significantly higher follow-up fasting blood glucose levels (p = 0.001) and higher baseline and follow-up HbA1c levels (p = 0.0025 and p = 0.001, respectively), as well as a 4.5-fold increased risk of developing DM compared with other groups. Smoking significantly modified genetic risk, with smokers in the very high-risk group showing a 25% higher likelihood of developing DM. CDKAL1 and TCF7L2 variants were most prevalent in the moderate- and high-risk groups, while HHEX variants in the high-risk group showed the greatest susceptibility, particularly among current smokers. Overall, PRS-based genetic testing demonstrated potential clinical utility for stratifying individuals according to relative diabetes risk, highlighting a possible interaction between genetic susceptibility and lifestyle factors such as smoking