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Article

Age by Single Nucleotide Polymorphism Interactions on Bronchodilator Response in Asthmatics

1
Department of Population Medicine, Harvard Pilgrim Health Care Institute and Harvard Medical School, Boston, MA 02215, USA
2
Channing Division of Network Medicine, Brigham and Women’s Hospital, Boston, MA 02115, USA
3
Department of Internal Medicine, Wake Forest School of Medicine, Winston-Salem, NC 27101, USA
4
Division of Pediatric Respiratory Medicine, Department of Pediatrics, University of California San Diego, San Diego, CA 92093, USA
5
Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, MA 02115, USA
6
Division of General Pediatrics, Department of Pediatrics, Children’s Hospital, Boston, MA 02215, USA
*
Author to whom correspondence should be addressed.
These authors contributed equally to this publication.
These authors contributed equally to this publication.
J. Pers. Med. 2021, 11(1), 59; https://doi.org/10.3390/jpm11010059
Received: 7 December 2020 / Revised: 10 January 2021 / Accepted: 12 January 2021 / Published: 19 January 2021
(This article belongs to the Special Issue APAA: Asthma Pharmacogenetics across Ages)
An unaddressed and important issue is the role age plays in modulating response to short acting β2-agonists in individuals with asthma. The objective of this study was to identify whether age modifies genetic associations of single nucleotide polymorphisms (SNPs) with bronchodilator response (BDR) to β2-agonists. Using three cohorts with a total of 892 subjects, we ran a genome wide interaction study (GWIS) for each cohort to examine SNP by age interactions with BDR. A fixed effect meta-analysis was used to combine the results. In order to determine if previously identified BDR SNPs had an age interaction, we also examined 16 polymorphisms in candidate genes from two published genome wide association studies (GWAS) of BDR. There were no significant SNP by age interactions on BDR using the genome wide significance level of 5 × 10−8. Using a suggestive significance level of 5 × 10−6, three interactions, including one for a SNP within PRAG1 (rs4840337), were significant and replicated at the significance level of 0.05. Considering candidate genes from two previous GWAS of BDR, three SNPs (rs10476900 (near ADRB2) [p-value = 0.009], rs10827492 (CREM) [p-value = 0.02], and rs72646209 (NCOA3) [p-value = 0.02]) had a marginally significant interaction with age on BDR (p < 0.05). Our results suggest age may be an important modifier of genetic associations for BDR in asthma. View Full-Text
Keywords: bronchodilator response; genome-wide interaction study; asthma bronchodilator response; genome-wide interaction study; asthma
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MDPI and ACS Style

Voorhies, K.; Sordillo, J.E.; McGeachie, M.; Ampleford, E.; Wang, A.L.; Lasky-Su, J.; Tantisira, K.; Dahlin, A.; Kelly, R.S.; Ortega, V.E.; Lutz, S.M.; Wu, A.C. Age by Single Nucleotide Polymorphism Interactions on Bronchodilator Response in Asthmatics. J. Pers. Med. 2021, 11, 59. https://doi.org/10.3390/jpm11010059

AMA Style

Voorhies K, Sordillo JE, McGeachie M, Ampleford E, Wang AL, Lasky-Su J, Tantisira K, Dahlin A, Kelly RS, Ortega VE, Lutz SM, Wu AC. Age by Single Nucleotide Polymorphism Interactions on Bronchodilator Response in Asthmatics. Journal of Personalized Medicine. 2021; 11(1):59. https://doi.org/10.3390/jpm11010059

Chicago/Turabian Style

Voorhies, Kirsten, Joanne E. Sordillo, Michael McGeachie, Elizabeth Ampleford, Alberta L. Wang, Jessica Lasky-Su, Kelan Tantisira, Amber Dahlin, Rachel S. Kelly, Victor E. Ortega, Sharon M. Lutz, and Ann C. Wu 2021. "Age by Single Nucleotide Polymorphism Interactions on Bronchodilator Response in Asthmatics" Journal of Personalized Medicine 11, no. 1: 59. https://doi.org/10.3390/jpm11010059

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