| Title: | Multiancestral polygenic risk score for pediatric asthma |
| Journal: | Journal of Allergy and Clinical Immunology |
| Published: | 18 May 2022 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/35595084/ |
| DOI: | https://doi.org/10.1016/j.jaci.2022.03.035 |
| URL: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9643615 |
| Citations: | 20 (18 in last 2 years) as of 8 Aug 2024 |
Publication 12369
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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.</p>
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.</p>
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.</p>
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, PFDR = 3.71 × 10-65) and related phenotypes.</p>
CONCLUSIONS: A multiancestral PRS for asthma based on Bayesian posterior genomic effect sizes identifies increased odds of pediatric asthma.</p>
9 Keywords
- Asthma
- Bayes Theorem
- Child
- Genetic Predisposition to Disease
- Genome-Wide Association Study
- Humans
- Multifactorial Inheritance
- Polymorphism, Single Nucleotide
- Risk Factors
25 Authors
- 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
1 Application
| Application ID | Title |
|---|---|
| 47377 | Improved Polygenic Risk Score Calculation and Sub-classification of Disease by the Incorporation of Functional Data. |
Enabling scientific discoveries that improve human health