Assessment of genetic factor and depression interactions for asthma symptom severity in cohorts of childhood and elderly asthmatics
Author
Park, Heung-WooSong, Woo-Jung
Cho, Sang-Heon
McGeachie, Michael J.
Martinez, Fernando
Mauger, Dave
Bender, Bruce G.
Tantisira, Kelan G.
Affiliation
Univ Arizona, Arizona Resp CtrIssue Date
2018-07-04
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NATURE PUBLISHING GROUPCitation
Park, H. W., Song, W. J., Cho, S. H., McGeachie, M. J., Martinez, F., Mauger, D., ... & Tantisira, K. G. (2018). Assessment of genetic factor and depression interactions for asthma symptom severity in cohorts of childhood and elderly asthmatics. Experimental & molecular medicine, 50(7), 77.Rights
© The Author(s) 2018. This article is licensed under a Creative Commons Attribution 4.0 International License.Collection Information
This item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at repository@u.library.arizona.edu.Abstract
It is well known that depression is associated with asthma symptoms. We assessed the combined effects of genetic factors and depression on asthma symptom severity using Bayesian network (BN) analysis. The common 100 top-ranked single-nucleotide polymorphisms (SNPs) were obtained from two genome-wide association studies of symptom severity in two childhood asthmatics trials (CAMP (Childhood Asthma Management Program) and CARE (Childhood Asthma Research and Education)). Using SNPs plus five discretized variables (depression, anxiety, age, sex, and race), we performed BN analysis in 529 CAMP subjects. We identified two nodes (depression and rs4672619 mapping to ERBB4 (Erb-B2 receptor tyrosine kinase 4)) that were within the Markov neighborhood of the symptom node in the network and then evaluated the interactive effects of depressive status and rs4672619 genotypes on asthma symptom severity. In childhood asthmatics with homozygous reference alleles, severe depression was related to less severe symptoms. However, in childhood asthmatics with heterozygous alleles and homozygous variant alleles, depression and symptom severity showed a positive correlation (interaction permutation P value =0.019). We then tried to evaluate whether the interactive effects that we found were sustained in another independent cohort of elderly asthmatics. Contrary to the findings from childhood asthmatics, elderly asthmatics with homozygous reference alleles showed a positive correlation between depression and symptom severity, and elderly asthmatics with heterozygous alleles and homozygous variant alleles showed a negative correlation (interaction permutation P value =0.003). In conclusion, we have identified a novel SNP, rs4672619, that shows interactive effects with depression on asthma symptom severity in childhood and elderly asthmatics in opposite directions.Note
Open access journal.ISSN
2092-6413PubMed ID
29973587Version
Final published versionSponsors
National Institutes of Health, US [R01 NR013391, R01 HL127332, U01 HL065899]; Ministry of Health and Welfare, Republic of Korea [2008-E33028-00, 2009-E33022-00, 2011-E33005-00]; Parker B. Francis FoundationAdditional Links
http://www.nature.com/articles/s12276-018-0110-5ae974a485f413a2113503eed53cd6c53
10.1038/s12276-018-0110-5
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Except where otherwise noted, this item's license is described as © The Author(s) 2018. This article is licensed under a Creative Commons Attribution 4.0 International License.
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