Introduction
Asthma remains the most prevalent chronic condition among children, significantly impacting their quality of life and leading to considerable healthcare utilization. Traditional methods for predicting asthma, largely based on clinical signs and family history, have provided limited insights, particularly across diverse populations. This blog delves into the innovative approach of using a multiancestral polygenic risk score (PRS) for pediatric asthma, which utilizes comprehensive genetic analysis to predict asthma risk more accurately across different ancestries.
The Need for a Multiancestral Approach
Asthma is influenced by both environmental and genetic factors, but the interplay between these can vary significantly across different racial and ethnic groups. Most existing genetic studies and resultant PRSs focus predominantly on populations of European descent, which limits their applicability on a global scale. Recognizing this gap, the study incorporates a wide array of genetic data from diverse populations to develop a more universally applicable PRS.
Understanding the Polygenic Risk Score (PRS)
The Development of Multiancestral Asthma PRS
The research utilized genetic data from the Trans-National Asthma Genetic Consortium, which includes 985,837 genetic variants identified as relevant for asthma risk. The approach leverages a Bayesian regression framework, integrating data from multiple ancestries to enhance the predictive accuracy of the PRS across diverse populations.
Training and Validation of the PRS
The PRS was trained using data from the eMERGE network and validated against two independent cohorts, including the UK Biobank, enhancing the robustness and reliability of the score. The validation process confirmed the PRS’s efficacy in predicting pediatric-onset asthma across various ancestries.
![Assessment of Multiancestral Polygenic Risk Score Efficacy in Pediatric Asthma Cohorts ROC curves displaying the performance of the Multiancestral Polygenic Risk Score (PRS) in three pediatric cohorts: Training, Validation 1, and Validation 2.](https://i0.wp.com/mvlabs.ai/wp-content/uploads/2024/05/051324-Post-Fig-2.jpg?resize=283%2C300&ssl=1)
![Comparison of PRS Percentiles Between Controls and Pediatric Asthma Cases Across Different Cohorts Violin plots comparing the PRS percentiles between controls and pediatric asthma cases across three cohorts: Training, Validation 1, and Validation 2.](https://i0.wp.com/mvlabs.ai/wp-content/uploads/2024/05/051324-Post-Fig-3.jpg?resize=133%2C300&ssl=1)
![Phenome-Wide Association Study of Asthma Polygenic Risk Score Manhattan plot showing the PheWAS analysis results of the asthma polygenic risk score across various phenotypes in combined training and validation cohorts.](https://i0.wp.com/mvlabs.ai/wp-content/uploads/2024/05/051324-Post-Fig-4.jpg?resize=300%2C159&ssl=1)
Application of the Multiancestral PRS in Clinical Settings
The practical application of this PRS can revolutionize preventive strategies in pediatric asthma. By identifying at-risk children early, particularly in underserved populations, healthcare providers can tailor interventions more effectively and potentially reduce the incidence of asthma exacerbations.
Challenges and Considerations
While the multiancestral PRS presents a significant advancement in asthma prediction, there are challenges to consider:
- Complexity of Asthma as a Disease: Asthma is a complex disease with a myriad of contributing factors. The PRS, while powerful, is not the sole solution but should be integrated with other clinical data to optimize patient care.
- Ethical and Social Implications: The use of genetic information in predicting disease risk raises ethical questions, particularly concerning privacy, data security, and the potential for genetic discrimination.
Future Directions
The study sets the stage for further research, particularly in integrating this PRS with other biomarkers and environmental data to develop a comprehensive risk assessment tool for asthma. Future studies could also explore the application of similar PRS models for other complex diseases.
Conclusion
The development of a multiancestral PRS for pediatric asthma represents a significant leap forward in our ability to predict and manage this challenging disease across diverse populations. It highlights the critical need for incorporating genetic diversity into medical research, ultimately paving the way for more personalized and effective healthcare interventions.
Other Figures
![Analysis of Polygenic Risk Score Distribution by Ancestry and Adjustment Effects A composite image displaying a principal component plot by ancestry and two density plots showing the distribution of polygenic risk scores (PRS) before and after adjustment for principal components.](https://i0.wp.com/mvlabs.ai/wp-content/uploads/2024/05/051324-Post-Fig-5.jpg?resize=278%2C300&ssl=1)
![Odds of Asthma Across PRS Deciles in Different Cohorts Three dot plots representing the odds of asthma risk across PRS deciles in the Training, Validation 1, and Validation 2 cohorts.](https://i0.wp.com/mvlabs.ai/wp-content/uploads/2024/05/051324-Post-Fig-E2-300x75.jpg?resize=300%2C75&ssl=1)
![Comparison of Asthma Risk Prediction Across Studies for AMR and AFR Populations Bar graphs comparing the odds ratios per standard deviation of asthma risk scores between two previous studies (PGS1 and PGS2) and the current study for AMR and AFR populations.](https://i0.wp.com/mvlabs.ai/wp-content/uploads/2024/05/051324-Post-Fig-E3-300x152.jpg?resize=300%2C152&ssl=1)
![Gender and Ancestry Differences in Predicted Asthma Risk from Multiancestral PRS Line graphs showing the marginal predicted risk of asthma across standard deviations of adjusted multiancestral polygenic risk scores (PRS) for different genders and ancestries.](https://i0.wp.com/mvlabs.ai/wp-content/uploads/2024/05/051324-Post-Fig-E4-300x94.jpg?resize=300%2C94&ssl=1)