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Human genetics provides a profound framework for understanding the interplay between genetic predispositions and human psychology. At the heart of this discipline lies the study of how genes influence physical traits, behaviors, and susceptibility to diseases. Each person carries a unique genetic code that subtly or significantly shapes their psychological and behavioral landscape.
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Related Experiment Video

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Mediation of Polygenic Asthma Risk Through Gene Expression.

Rakesh Natarajan1, Brooke Szczesny1, Kanika Kanchan1

  • 1Genomics and Precision Health Section, Laboratory of Allergic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA.

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Summary

The best polygenic risk score (PRS) for asthma in African-ancestry populations was identified using the largest sample size. This PRS

Keywords:
African ancestriesGWASIgET2 inflammationasthmaeosinophilsgene expressionmedication responsepolygenic risk scoreswound healing

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Area of Science:

  • Genetics
  • Asthma Research
  • Population Genetics

Background:

  • Existing asthma polygenic risk scores (PRSs) lack validation in African-ancestry populations.
  • This limits understanding of PRS applicability across diverse ancestries.
  • Investigating PRS performance in African-ancestry individuals is crucial for equitable genomic medicine.

Purpose of the Study:

  • To evaluate the performance of published asthma PRSs in African-ancestry individuals.
  • To determine the extent to which PRS-asthma associations are mediated by clinical and gene-expression biomarkers.

Main Methods:

  • Applied 22 PRSs from the PGS Catalog in 673 African-ancestry individuals (CAAPA cohort).
  • Calculated mediation by clinical biomarkers (e.g., IgE, eosinophils) and nasal epithelium gene expression.
  • Defined asthma as a doctor's diagnosis; restricted cases to current disease for gene expression analysis.

Main Results:

  • The best-performing PRS (PGS001782) was derived from the largest African-ancestry dataset.
  • PRS effect on asthma was significantly mediated by total IgE (38.8%), specific IgE (38.7%), and eosinophils (7.3%).
  • Gene expression mediation involved T2 inflammation (21.9%), wound healing (11.9%), and medication response (6.8%) modules.

Conclusions:

  • The PRS developed with the largest African-ancestry sample size demonstrated the best performance.
  • Mediation analysis supports the biological pathways of T2 inflammation, wound healing, and medication response in asthma.
  • Findings highlight the importance of ancestry-specific PRS development for improved asthma prediction.