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Interweaving between genetic and epigenetic studies on childhood asthma

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 (r2 < 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
2516-8657
Rathod, Aniruddha
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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
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).

Record type: Article

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 (r2 < 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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Accepted/In Press date: 8 April 2020
Published date: 22 July 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
ORCID for John W Holloway: ORCID iD orcid.org/0000-0001-9998-0464

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Date deposited: 20 Aug 2020 16:30
Last modified: 26 Nov 2021 02:40

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Contributors

Author: Aniruddha Rathod
Author: Jiasong Duan
Author: Hongmei Zhang
Author: John W Holloway ORCID iD
Author: Susan Ewart
Author: Syed Arshad
Author: Wilfried Karmaus

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