Multiancestral polygenic risk score for pediatric asthma

Disease areas:

• lungs

Last updated:

2 July 2025

Author(s):

Bahram Namjou, Michael Lape, Edyta Malolepsza, Stanley B. DeVore, Matthew T. Weirauch, Ozan Dikilitas, Gail P. Jarvik, Krzysztof Kiryluk, Iftikhar J. Kullo, Cong Liu, Yuan Luo, Benjamin A. Satterfield, Jordan W. Smoller, Theresa L. Walunas, John Connolly, Patrick Sleiman, Tesfaye B. Mersha, Frank D. Mentch, Hakon Hakonarson, Cynthia A. Prows, Jocelyn M. Biagini, Gurjit K. Khurana Hershey, Lisa J. Martin, Leah Kottyan, The eMERGE Network

Publish date:

18 May 2022

Journal:

Journal of Allergy and Clinical Immunology

PubMed ID:

35595084

DOI:

10.1016/j.jaci.2022.03.035

Abstract

BACKGROUND: Asthma is the most common chronic condition in children and the third leading cause of hospitalization in pediatrics. The genome-wide association study catalog reports 140 studies with genome-wide significance. A polygenic risk score (PRS) with predictive value across ancestries has not been evaluated for this important trait.

OBJECTIVES: This study aimed to train and validate a PRS relying on genetic determinants for asthma to provide predictions for disease occurrence in pediatric cohorts of diverse ancestries.

METHODS: This study applied a Bayesian regression framework method using the Trans-National Asthma Genetic Consortium genome-wide association study summary statistics to derive a multiancestral PRS score, used one Electronic Medical Records and Genomics (eMERGE) cohort as a training set, used a second independent eMERGE cohort to validate the score, and used the UK Biobank data to replicate the findings. A phenome-wide association study was performed using the PRS to identify shared genetic etiology with other phenotypes.

RESULTS: The multiancestral asthma PRS was associated with asthma in the 2 pediatric validation datasets. Overall, the multiancestral asthma PRS has an area under the curve (AUC) of 0.70 (95% CI, 0.69-0.72) in the pediatric validation 1 and AUC of 0.66 (0.65-0.66) in the pediatric validation 2 datasets. We found significant discrimination across pediatric subcohorts of European (AUC, 95% CI, 0.60 and 0.66), African (AUC, 95% CI, 0.61 and 0.66), admixed American (AUC, 0.64 and 0.70), Southeast Asian (AUC, 0.65), and East Asian (AUC, 0.73) ancestry. Pediatric participants with the top 5% PRS had 2.80 to 5.82 increased odds of asthma compared to the bottom 5% across the training, validation 1, and validation 2 cohorts when adjusted for ancestry. Phenome-wide association study analysis confirmed the strong association of the identified PRS with asthma (odds ratio, 2.71, P_FDR = 3.71 × 10^-65) and related phenotypes.

CONCLUSIONS: A multiancestral PRS for asthma based on Bayesian posterior genomic effect sizes identifies increased odds of pediatric asthma.