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Stratifying Lung Adenocarcinoma Risk with Multi-ancestry Polygenic Risk Scores in East Asian Never-Smokers.
Batel Blechter1, Xiaoyu Wang1, Jianxin Shi2,3
1Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD, USA.
Medrxiv : the Preprint Server for Health Sciences
|July 9, 2024
Summary
Developing multi-ancestry polygenic risk scores (PRS) improves lung adenocarcinoma (LUAD) risk prediction in East Asian never-smokers. This approach enhances risk stratification for LUAD in this population.
Area of Science:
- Genetics and Genomics
- Cancer Epidemiology
- Personalized Medicine
Background:
- Polygenic risk scores (PRS) are valuable for disease risk stratification.
- Current PRS are predominantly developed in European populations, limiting their application in diverse ancestries.
- Lung adenocarcinoma (LUAD) risk stratification in East Asian (EAS) never-smokers requires ancestry-specific or multi-ancestry PRS.
Purpose of the Study:
- To develop and evaluate single- and multi-ancestry polygenic risk scores (PRS) for lung adenocarcinoma (LUAD) in East Asian never-smokers.
- To assess the performance of these PRS in predicting LUAD risk within the East Asian population.
- To explore the potential of multi-ancestry PRS for improved LUAD risk stratification.
Main Methods:
- Utilized genome-wide association study (GWAS) summary statistics from East Asian (8,002 cases; 20,782 controls) and European (2,058 cases; 5,575 controls) populations.
- Developed single- and multi-ancestry PRS for LUAD.
- Employed the CT-SLEB method for multi-ancestry PRS development.
- Evaluated PRS performance using logistic regression and receiver operating characteristic (ROC) analysis.
Main Results:
- A multi-ancestry PRS demonstrated a strong association with LUAD risk (OR=1.71, 95% CI: 1.61-1.82).
- The area under the ROC curve for the multi-ancestry PRS was 0.640 (95% CI: 0.629-0.653).
- Individuals in the highest PRS quintile had nearly four times the LUAD risk compared to the lowest quintile.
- The 95th percentile of the PRS indicated an estimated 6.69% lifetime absolute risk, with average 10-year risk achieved decades earlier.
Conclusions:
- Multi-ancestry PRS approaches show significant potential for enhancing LUAD risk stratification in East Asian never-smokers.
- Developed PRS can identify individuals at substantially elevated LUAD risk.
- This study highlights the importance of considering ancestry in PRS development for equitable risk prediction.
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