Interweaving between genetic and epigenetic studies on childhood asthma
Interweaving between genetic and epigenetic studies on childhood asthma
The cause and underlying mechanisms that contribute to asthma pathogenesis are not well known. Both genome- and epigenome-wide association studies have identified genes associated with asthma risk. It is unknown to what extent genes identified in these two types of studies overlap. Based on existing literature and the DisGeNET database, we extracted overlapping genes identified in genetic and epigenetic studies of childhood asthma. Through analyses of variance, we assessed whether DNA methylation (DNAm) at 5′-C-phosphate-G-3′ (CpGs) on the overlapping genes was associated with neighboring single-nucleotide polymorphisms (SNPs) within 1M base pairs (bps) and with low linkage disequilibrium (r
2 < 0.2) in the childhood asthma-related genes. In total, 285 genes from genetic studies and 226 genes from epigenetic studies were shown to be associated with asthma risk, of which six overlap. Of the six genes, 79 CpGs and 8229 unique neighboring SNPs (1M bps) were included in methylation quantitative loci (methQTL) assessment analyses. We tested the association of DNAm at each of the 79 CpG sites with its neighboring SNPs. After adjusting for multiple testing by controlling the false discovery rate to 0.05 when testing methQTL for each CpG site, we found statistically significant associations in three genes with their neighboring SNPs and identified 34 unique methQTLs. The rather limited overlap in genes between genetic and epigenetic studies on asthma and the absence of methQTL in some of the overlapping genes highlight a need to jointly, rather than independently, examine genetic and epigenetic effects on asthma risk to improve our understanding of the underlying mechanisms of asthma.
DNA methylation, Genetic, SNPs, asthma, epigenetic, methQTLs
Rathod, Aniruddha
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Duan, Jiasong
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Zhang, Hongmei
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Holloway, John W
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Ewart, Susan
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Arshad, Syed
917e246d-2e60-472f-8d30-94b01ef28958
Karmaus, Wilfried
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22 July 2020
Rathod, Aniruddha
ad171ed4-9a16-436d-8811-26930180288b
Duan, Jiasong
c8f2e3fe-413f-4cd5-9a1c-28830d36ef04
Zhang, Hongmei
9f774048-54d6-4321-a252-3887b2c76db0
Holloway, John W
4bbd77e6-c095-445d-a36b-a50a72f6fe1a
Ewart, Susan
28667421-3cf7-43d7-b1c3-ca27564938f7
Arshad, Syed
917e246d-2e60-472f-8d30-94b01ef28958
Karmaus, Wilfried
281d0e53-6b5d-4d38-9732-3981b07cd853
Rathod, Aniruddha, Duan, Jiasong, Zhang, Hongmei, Holloway, John W, Ewart, Susan, Arshad, Syed and Karmaus, Wilfried
(2020)
Interweaving between genetic and epigenetic studies on childhood asthma.
Epigenetics Insights, 13.
(doi:10.1177/2516865720923395).
Abstract
The cause and underlying mechanisms that contribute to asthma pathogenesis are not well known. Both genome- and epigenome-wide association studies have identified genes associated with asthma risk. It is unknown to what extent genes identified in these two types of studies overlap. Based on existing literature and the DisGeNET database, we extracted overlapping genes identified in genetic and epigenetic studies of childhood asthma. Through analyses of variance, we assessed whether DNA methylation (DNAm) at 5′-C-phosphate-G-3′ (CpGs) on the overlapping genes was associated with neighboring single-nucleotide polymorphisms (SNPs) within 1M base pairs (bps) and with low linkage disequilibrium (r
2 < 0.2) in the childhood asthma-related genes. In total, 285 genes from genetic studies and 226 genes from epigenetic studies were shown to be associated with asthma risk, of which six overlap. Of the six genes, 79 CpGs and 8229 unique neighboring SNPs (1M bps) were included in methylation quantitative loci (methQTL) assessment analyses. We tested the association of DNAm at each of the 79 CpG sites with its neighboring SNPs. After adjusting for multiple testing by controlling the false discovery rate to 0.05 when testing methQTL for each CpG site, we found statistically significant associations in three genes with their neighboring SNPs and identified 34 unique methQTLs. The rather limited overlap in genes between genetic and epigenetic studies on asthma and the absence of methQTL in some of the overlapping genes highlight a need to jointly, rather than independently, examine genetic and epigenetic effects on asthma risk to improve our understanding of the underlying mechanisms of asthma.
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Interweaving Between Genetic and Epigenetic Studies
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Accepted/In Press date: 8 April 2020
Published date: 22 July 2020
Additional Information:
Funding Information:
The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This work was supported by the National Institutes of Health (grant numbers R01 AI121226, R01 HL132321).
Publisher Copyright:
© The Author(s) 2020.
Keywords:
DNA methylation, Genetic, SNPs, asthma, epigenetic, methQTLs
Identifiers
Local EPrints ID: 443286
URI: http://eprints.soton.ac.uk/id/eprint/443286
ISSN: 2516-8657
PURE UUID: 1e24d498-06a5-477d-af6a-2161a76711cd
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Date deposited: 20 Aug 2020 16:30
Last modified: 17 Mar 2024 02:45
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Contributors
Author:
Aniruddha Rathod
Author:
Jiasong Duan
Author:
Hongmei Zhang
Author:
Susan Ewart
Author:
Wilfried Karmaus
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