#0752
Genetic Risk and Biochemical Signatures for Urolithiasis Risk Prediction: A Cross-cohort Study in the United Kingdom and Hong Kong
Y. Zhan1, R. Ma1, R. Shi1, X. Ruan2, C. Yao1, S. Ali1, T. Chun1, A. Ng3, R. Na1
1The
University of Hong Kong, Department of Surgery, Hong Kong, Hong Kong, China
2Ruijin Hospital Affiliated to Shanghai Jiao Tong University School
of Medicine, Department of Urology, Shanghai, China
3Queen Mary Hospital, Department of Surgery, Hong Kong, Hong Kong,
China
Introduction:
Urolithiasis, a multifactorial disease with high recurrence, lacks robust tools for personalized risk prediction. While genetic susceptibility and biochemical changes are implicated in pathogenesis, their combined utility remains unexplored. This study aims to evaluate the integration of polygenic risk scores (PRS) and biomarker-derived signatures in predicting risks of incident, recurrent and multifocal urolithiasis across diverse populations.
Material and methods:
A cross-cohort study was implemented utilizing data of 480,098 participants from the UK Biobank (UKB) and 6,177 participants from the electronic health record database of Hong Kong Hospital Authority (EHR-HK). 16 biochemical markers related to urolithiasis were identified by LASSO regression. K-means clustering analysis was performed to categorize participants into biomarker-derived clusters. PRS was computed using genome-wide significant variants.
Results:
In UKB, 6,434 incident, 2,652 recurrent, and 777 multifocal urolithiasis cases were recorded respectively after a median follow-up of 13.8 years. Three biomarker signatures were identified, namely cardiovascular-skeletal (C-S), hematal-endocrine (H-E) and inflammatory-metabolic (I-M) clusters. Synergistic effects between PRS and biomarker signatures were observed: participants with top PRS quartile combined with I-M cluster had the highest risks of incident (hazard ratio [HR]=2.66, 95% confidence interval [CI]: 2.43-2.90), recurrent (3.56 [3.11-4.08]), and multifocal urolithiasis (2.94 [2.29-3.78]) compared to the lowest-risk group (PRS Q1 + C-S cluster) (Figure 1). Validation in EHR-HK with 1,304 incident, 263 recurrent, and 233 multifocal urolithiasis cases confirmed elevated urolithiasis odds for I-M (odds ratio [OR]=1.32, 95%CI: 1.19-1.47) and H-E clusters (1.11 [1.00-1.22]) compared to C-S cluster.