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Related Concept Videos

Polygenic Traits01:18

Polygenic Traits

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When more than one gene is responsible for a given phenotype, the trait is considered polygenic. Human height is a polygenic trait. Studies have uncovered hundreds of loci that influence height, and there are believed to be many more. Due to the high number of genes involved, as well as environmental and nutritional factors, height varies significantly within a given population. The distribution of height forms a bell-shaped curve, with relatively few individuals in the population at the...
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Asthma is a prevalent chronic respiratory condition marked by inflammation and hyperresponsiveness of the airways. Its pathophysiology involves complex interactions among inflammatory pathways, immune responses, and neural mechanisms.
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Multiancestral polygenic risk score for pediatric asthma.

Bahram Namjou1, Michael Lape2, Edyta Malolepsza3

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A new polygenic risk score (PRS) effectively identifies children at increased risk for asthma across diverse ancestries. This genetic tool aids in predicting asthma occurrence and understanding its genetic links.

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Area of Science:

  • Genetics
  • Pediatrics
  • Computational Biology

Background:

  • Asthma is a leading chronic condition and cause of hospitalization in children.
  • Existing genome-wide association studies (GWAS) have identified numerous genetic loci for asthma.
  • A polygenic risk score (PRS) with predictive value across diverse ancestries for asthma has not been established.

Purpose of the Study:

  • To develop and validate a multiancestral PRS for predicting asthma in pediatric populations.
  • To assess the PRS's predictive performance across various ancestral groups.
  • To explore shared genetic etiology between asthma and other phenotypes using the PRS.

Main Methods:

  • Utilized a Bayesian regression framework and GWAS summary statistics from the Trans-National Asthma Genetic Consortium.
  • Trained the PRS on one Electronic Medical Records and Genomics (eMERGE) cohort and validated it on a second independent eMERGE cohort.
  • Replicated findings using UK Biobank data and performed phenome-wide association studies (PheWAS) with the PRS.

Main Results:

  • The multiancestral asthma PRS demonstrated significant association with asthma in pediatric validation datasets (AUCs ranging from 0.66 to 0.70).
  • The PRS showed predictive capability across diverse ancestries, including European, African, admixed American, Southeast Asian, and East Asian populations.
  • Individuals in the top 5% PRS had significantly increased odds of asthma (2.80-5.82 times) compared to the bottom 5%.

Conclusions:

  • A multiancestral PRS derived from Bayesian posterior genomic effect sizes effectively identifies increased odds of pediatric asthma.
  • The developed PRS holds potential for predicting asthma risk in diverse pediatric cohorts.
  • The PRS also highlights shared genetic underpinnings with other asthma-related phenotypes.