The interaction of genetic variants and DNA methylation of the interleukin-4 receptor gene increase the risk of asthma at age 18 years

<p<Abstract</p< <p<Background</p< <p<The occurrence of asthma is weakly explained by known genetic variants. Epigenetic marks, DNA methylation (DNA-M) in particular, are considered to add to the explanation of asthma. However, no etiological model has yet been developed that integrates genetic variants and DNA-M. To explore a new model, we focused on one asthma candidate gene, the IL-4 receptor (<it<IL4R</it<). We hypothesized that genetic variants of <it<IL4R</it< in interaction with DNA-M at cytosine-phosphate-guanine (CpG) sites jointly alter the risk of asthma during adolescence. Blood samples were collected at age 18 years from 245 female cohort participants randomly selected for methylation analysis from a birth cohort (n = 1,456, Isle of Wight, UK). Genome-wide DNA-M was assessed using the Illumina Infinium HumanMethylation450 BeadChip.</p< <p<Results</p< <p<Thirteen single nucleotide polymorphisms (SNPs) and twelve CpG sites of <it<IL4R</it< gene were analyzed. Based on linkage disequilibrium and association with asthma, eight SNPs and one CpG site were selected for further analyses. Of the twelve CpG sites in the <it<IL4R</it< gene, only methylation levels of cg09791102 showed an association with asthma at age 18 years (Wilcoxon test: <it<P</it< = 0.01). Log-linear models were used to estimate risk ratios (RRs) for asthma adjusting for uncorrelated SNPs within the <it<IL4R</it< gene and covariates. Testing for interaction between the eight SNPs and the methylation levels of cg09791102 on the risk for asthma at age 18 years, we identified the statistically significant interaction term of SNP rs3024685 × methylation levels of cg09791102 (<it<P</it< = 0.002; after adjusting for false discovery rate). A total of 84 participants had methylation levels ≤0.88, 112 participants between 0.89 and 0.90, and 35 between 0.91 and 0.92. For the SNP rs3024685 (‘CC’ vs. ‘TT’) at methylation levels of ≤0.85, 0.86, 0.90, 0.91, and 0.92, the RRs were 0.01, 0.04, 4.65, 14.76, 14.90, respectively (interaction effect, <it<P</it< = 0.0003).</p< <p<Conclusions</p< <p<Adjusting for multiple testing, our results suggest that DNA-M modulates the risk of asthma related to genetic variants in the <it<IL4R</it< gene. The strong interaction of one SNP and DNA-M is encouraging and provides a novel model of how a joint effect of genetic variants and DNA-M can explain occurrence of asthma.</p< Ausführliche Beschreibung

Gespeichert in:

Autor*in:	Soto-Ramírez Nelís [verfasserIn] Arshad Syed Hasan [verfasserIn] Holloway John W [verfasserIn] Zhang Hongmei [verfasserIn] Schauberger Eric [verfasserIn] Ewart Susan [verfasserIn] Patil Veeresh [verfasserIn] Karmaus Wilfried [verfasserIn]

Format:	E-Artikel
Sprache:	Englisch

Erschienen:	2013

Schlagwörter:	Interleukin-4 receptor gene DNA methylation Genetic variants Asthma Epigenetics

Übergeordnetes Werk:	In: Clinical Epigenetics - BMC, 2012, 5(2013), 1, p 1
Übergeordnetes Werk:	volume:5 ; year:2013 ; number:1, p 1

Links:	Link aufrufen Link aufrufen Link aufrufen Journal toc

DOI / URN:	10.1186/1868-7083-5-1

Katalog-ID:	DOAJ064994058

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520			\|a <p<Abstract</p< <p<Background</p< <p<The occurrence of asthma is weakly explained by known genetic variants. Epigenetic marks, DNA methylation (DNA-M) in particular, are considered to add to the explanation of asthma. However, no etiological model has yet been developed that integrates genetic variants and DNA-M. To explore a new model, we focused on one asthma candidate gene, the IL-4 receptor (<it<IL4R</it<). We hypothesized that genetic variants of <it<IL4R</it< in interaction with DNA-M at cytosine-phosphate-guanine (CpG) sites jointly alter the risk of asthma during adolescence. Blood samples were collected at age 18 years from 245 female cohort participants randomly selected for methylation analysis from a birth cohort (n = 1,456, Isle of Wight, UK). Genome-wide DNA-M was assessed using the Illumina Infinium HumanMethylation450 BeadChip.</p< <p<Results</p< <p<Thirteen single nucleotide polymorphisms (SNPs) and twelve CpG sites of <it<IL4R</it< gene were analyzed. Based on linkage disequilibrium and association with asthma, eight SNPs and one CpG site were selected for further analyses. Of the twelve CpG sites in the <it<IL4R</it< gene, only methylation levels of cg09791102 showed an association with asthma at age 18 years (Wilcoxon test: <it<P</it< = 0.01). Log-linear models were used to estimate risk ratios (RRs) for asthma adjusting for uncorrelated SNPs within the <it<IL4R</it< gene and covariates. Testing for interaction between the eight SNPs and the methylation levels of cg09791102 on the risk for asthma at age 18 years, we identified the statistically significant interaction term of SNP rs3024685 × methylation levels of cg09791102 (<it<P</it< = 0.002; after adjusting for false discovery rate). A total of 84 participants had methylation levels ≤0.88, 112 participants between 0.89 and 0.90, and 35 between 0.91 and 0.92. For the SNP rs3024685 (‘CC’ vs. ‘TT’) at methylation levels of ≤0.85, 0.86, 0.90, 0.91, and 0.92, the RRs were 0.01, 0.04, 4.65, 14.76, 14.90, respectively (interaction effect, <it<P</it< = 0.0003).</p< <p<Conclusions</p< <p<Adjusting for multiple testing, our results suggest that DNA-M modulates the risk of asthma related to genetic variants in the <it<IL4R</it< gene. The strong interaction of one SNP and DNA-M is encouraging and provides a novel model of how a joint effect of genetic variants and DNA-M can explain occurrence of asthma.</p<
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allfields	10.1186/1868-7083-5-1 doi (DE-627)DOAJ064994058 (DE-599)DOAJb21d793ebb8a49ea9da9c8ee5d160f37 DE-627 ger DE-627 rakwb eng QH426-470 Soto-Ramírez Nelís verfasserin aut The interaction of genetic variants and DNA methylation of the interleukin-4 receptor gene increase the risk of asthma at age 18 years 2013 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier <p<Abstract</p< <p<Background</p< <p<The occurrence of asthma is weakly explained by known genetic variants. Epigenetic marks, DNA methylation (DNA-M) in particular, are considered to add to the explanation of asthma. However, no etiological model has yet been developed that integrates genetic variants and DNA-M. To explore a new model, we focused on one asthma candidate gene, the IL-4 receptor (<it<IL4R</it<). We hypothesized that genetic variants of <it<IL4R</it< in interaction with DNA-M at cytosine-phosphate-guanine (CpG) sites jointly alter the risk of asthma during adolescence. Blood samples were collected at age 18 years from 245 female cohort participants randomly selected for methylation analysis from a birth cohort (n = 1,456, Isle of Wight, UK). Genome-wide DNA-M was assessed using the Illumina Infinium HumanMethylation450 BeadChip.</p< <p<Results</p< <p<Thirteen single nucleotide polymorphisms (SNPs) and twelve CpG sites of <it<IL4R</it< gene were analyzed. Based on linkage disequilibrium and association with asthma, eight SNPs and one CpG site were selected for further analyses. Of the twelve CpG sites in the <it<IL4R</it< gene, only methylation levels of cg09791102 showed an association with asthma at age 18 years (Wilcoxon test: <it<P</it< = 0.01). Log-linear models were used to estimate risk ratios (RRs) for asthma adjusting for uncorrelated SNPs within the <it<IL4R</it< gene and covariates. Testing for interaction between the eight SNPs and the methylation levels of cg09791102 on the risk for asthma at age 18 years, we identified the statistically significant interaction term of SNP rs3024685 × methylation levels of cg09791102 (<it<P</it< = 0.002; after adjusting for false discovery rate). A total of 84 participants had methylation levels ≤0.88, 112 participants between 0.89 and 0.90, and 35 between 0.91 and 0.92. For the SNP rs3024685 (‘CC’ vs. ‘TT’) at methylation levels of ≤0.85, 0.86, 0.90, 0.91, and 0.92, the RRs were 0.01, 0.04, 4.65, 14.76, 14.90, respectively (interaction effect, <it<P</it< = 0.0003).</p< <p<Conclusions</p< <p<Adjusting for multiple testing, our results suggest that DNA-M modulates the risk of asthma related to genetic variants in the <it<IL4R</it< gene. The strong interaction of one SNP and DNA-M is encouraging and provides a novel model of how a joint effect of genetic variants and DNA-M can explain occurrence of asthma.</p< Interleukin-4 receptor gene DNA methylation Genetic variants Asthma Epigenetics Medicine R Genetics Arshad Syed Hasan verfasserin aut Holloway John W verfasserin aut Zhang Hongmei verfasserin aut Schauberger Eric verfasserin aut Ewart Susan verfasserin aut Patil Veeresh verfasserin aut Karmaus Wilfried verfasserin aut In Clinical Epigenetics BMC, 2012 5(2013), 1, p 1 (DE-627)626459028 (DE-600)2553921-8 18687083 nnns volume:5 year:2013 number:1, p 1 https://doi.org/10.1186/1868-7083-5-1 kostenfrei https://doaj.org/article/b21d793ebb8a49ea9da9c8ee5d160f37 kostenfrei http://www.clinicalepigeneticsjournal.com/content/5/1/1 kostenfrei https://doaj.org/toc/1868-7083 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 5 2013 1, p 1
spelling	10.1186/1868-7083-5-1 doi (DE-627)DOAJ064994058 (DE-599)DOAJb21d793ebb8a49ea9da9c8ee5d160f37 DE-627 ger DE-627 rakwb eng QH426-470 Soto-Ramírez Nelís verfasserin aut The interaction of genetic variants and DNA methylation of the interleukin-4 receptor gene increase the risk of asthma at age 18 years 2013 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier <p<Abstract</p< <p<Background</p< <p<The occurrence of asthma is weakly explained by known genetic variants. Epigenetic marks, DNA methylation (DNA-M) in particular, are considered to add to the explanation of asthma. However, no etiological model has yet been developed that integrates genetic variants and DNA-M. To explore a new model, we focused on one asthma candidate gene, the IL-4 receptor (<it<IL4R</it<). We hypothesized that genetic variants of <it<IL4R</it< in interaction with DNA-M at cytosine-phosphate-guanine (CpG) sites jointly alter the risk of asthma during adolescence. Blood samples were collected at age 18 years from 245 female cohort participants randomly selected for methylation analysis from a birth cohort (n = 1,456, Isle of Wight, UK). Genome-wide DNA-M was assessed using the Illumina Infinium HumanMethylation450 BeadChip.</p< <p<Results</p< <p<Thirteen single nucleotide polymorphisms (SNPs) and twelve CpG sites of <it<IL4R</it< gene were analyzed. Based on linkage disequilibrium and association with asthma, eight SNPs and one CpG site were selected for further analyses. Of the twelve CpG sites in the <it<IL4R</it< gene, only methylation levels of cg09791102 showed an association with asthma at age 18 years (Wilcoxon test: <it<P</it< = 0.01). Log-linear models were used to estimate risk ratios (RRs) for asthma adjusting for uncorrelated SNPs within the <it<IL4R</it< gene and covariates. Testing for interaction between the eight SNPs and the methylation levels of cg09791102 on the risk for asthma at age 18 years, we identified the statistically significant interaction term of SNP rs3024685 × methylation levels of cg09791102 (<it<P</it< = 0.002; after adjusting for false discovery rate). A total of 84 participants had methylation levels ≤0.88, 112 participants between 0.89 and 0.90, and 35 between 0.91 and 0.92. For the SNP rs3024685 (‘CC’ vs. ‘TT’) at methylation levels of ≤0.85, 0.86, 0.90, 0.91, and 0.92, the RRs were 0.01, 0.04, 4.65, 14.76, 14.90, respectively (interaction effect, <it<P</it< = 0.0003).</p< <p<Conclusions</p< <p<Adjusting for multiple testing, our results suggest that DNA-M modulates the risk of asthma related to genetic variants in the <it<IL4R</it< gene. The strong interaction of one SNP and DNA-M is encouraging and provides a novel model of how a joint effect of genetic variants and DNA-M can explain occurrence of asthma.</p< Interleukin-4 receptor gene DNA methylation Genetic variants Asthma Epigenetics Medicine R Genetics Arshad Syed Hasan verfasserin aut Holloway John W verfasserin aut Zhang Hongmei verfasserin aut Schauberger Eric verfasserin aut Ewart Susan verfasserin aut Patil Veeresh verfasserin aut Karmaus Wilfried verfasserin aut In Clinical Epigenetics BMC, 2012 5(2013), 1, p 1 (DE-627)626459028 (DE-600)2553921-8 18687083 nnns volume:5 year:2013 number:1, p 1 https://doi.org/10.1186/1868-7083-5-1 kostenfrei https://doaj.org/article/b21d793ebb8a49ea9da9c8ee5d160f37 kostenfrei http://www.clinicalepigeneticsjournal.com/content/5/1/1 kostenfrei https://doaj.org/toc/1868-7083 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 5 2013 1, p 1
allfields_unstemmed	10.1186/1868-7083-5-1 doi (DE-627)DOAJ064994058 (DE-599)DOAJb21d793ebb8a49ea9da9c8ee5d160f37 DE-627 ger DE-627 rakwb eng QH426-470 Soto-Ramírez Nelís verfasserin aut The interaction of genetic variants and DNA methylation of the interleukin-4 receptor gene increase the risk of asthma at age 18 years 2013 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier <p<Abstract</p< <p<Background</p< <p<The occurrence of asthma is weakly explained by known genetic variants. Epigenetic marks, DNA methylation (DNA-M) in particular, are considered to add to the explanation of asthma. However, no etiological model has yet been developed that integrates genetic variants and DNA-M. To explore a new model, we focused on one asthma candidate gene, the IL-4 receptor (<it<IL4R</it<). We hypothesized that genetic variants of <it<IL4R</it< in interaction with DNA-M at cytosine-phosphate-guanine (CpG) sites jointly alter the risk of asthma during adolescence. Blood samples were collected at age 18 years from 245 female cohort participants randomly selected for methylation analysis from a birth cohort (n = 1,456, Isle of Wight, UK). Genome-wide DNA-M was assessed using the Illumina Infinium HumanMethylation450 BeadChip.</p< <p<Results</p< <p<Thirteen single nucleotide polymorphisms (SNPs) and twelve CpG sites of <it<IL4R</it< gene were analyzed. Based on linkage disequilibrium and association with asthma, eight SNPs and one CpG site were selected for further analyses. Of the twelve CpG sites in the <it<IL4R</it< gene, only methylation levels of cg09791102 showed an association with asthma at age 18 years (Wilcoxon test: <it<P</it< = 0.01). Log-linear models were used to estimate risk ratios (RRs) for asthma adjusting for uncorrelated SNPs within the <it<IL4R</it< gene and covariates. Testing for interaction between the eight SNPs and the methylation levels of cg09791102 on the risk for asthma at age 18 years, we identified the statistically significant interaction term of SNP rs3024685 × methylation levels of cg09791102 (<it<P</it< = 0.002; after adjusting for false discovery rate). A total of 84 participants had methylation levels ≤0.88, 112 participants between 0.89 and 0.90, and 35 between 0.91 and 0.92. For the SNP rs3024685 (‘CC’ vs. ‘TT’) at methylation levels of ≤0.85, 0.86, 0.90, 0.91, and 0.92, the RRs were 0.01, 0.04, 4.65, 14.76, 14.90, respectively (interaction effect, <it<P</it< = 0.0003).</p< <p<Conclusions</p< <p<Adjusting for multiple testing, our results suggest that DNA-M modulates the risk of asthma related to genetic variants in the <it<IL4R</it< gene. The strong interaction of one SNP and DNA-M is encouraging and provides a novel model of how a joint effect of genetic variants and DNA-M can explain occurrence of asthma.</p< Interleukin-4 receptor gene DNA methylation Genetic variants Asthma Epigenetics Medicine R Genetics Arshad Syed Hasan verfasserin aut Holloway John W verfasserin aut Zhang Hongmei verfasserin aut Schauberger Eric verfasserin aut Ewart Susan verfasserin aut Patil Veeresh verfasserin aut Karmaus Wilfried verfasserin aut In Clinical Epigenetics BMC, 2012 5(2013), 1, p 1 (DE-627)626459028 (DE-600)2553921-8 18687083 nnns volume:5 year:2013 number:1, p 1 https://doi.org/10.1186/1868-7083-5-1 kostenfrei https://doaj.org/article/b21d793ebb8a49ea9da9c8ee5d160f37 kostenfrei http://www.clinicalepigeneticsjournal.com/content/5/1/1 kostenfrei https://doaj.org/toc/1868-7083 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 5 2013 1, p 1
allfieldsGer	10.1186/1868-7083-5-1 doi (DE-627)DOAJ064994058 (DE-599)DOAJb21d793ebb8a49ea9da9c8ee5d160f37 DE-627 ger DE-627 rakwb eng QH426-470 Soto-Ramírez Nelís verfasserin aut The interaction of genetic variants and DNA methylation of the interleukin-4 receptor gene increase the risk of asthma at age 18 years 2013 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier <p<Abstract</p< <p<Background</p< <p<The occurrence of asthma is weakly explained by known genetic variants. Epigenetic marks, DNA methylation (DNA-M) in particular, are considered to add to the explanation of asthma. However, no etiological model has yet been developed that integrates genetic variants and DNA-M. To explore a new model, we focused on one asthma candidate gene, the IL-4 receptor (<it<IL4R</it<). We hypothesized that genetic variants of <it<IL4R</it< in interaction with DNA-M at cytosine-phosphate-guanine (CpG) sites jointly alter the risk of asthma during adolescence. Blood samples were collected at age 18 years from 245 female cohort participants randomly selected for methylation analysis from a birth cohort (n = 1,456, Isle of Wight, UK). Genome-wide DNA-M was assessed using the Illumina Infinium HumanMethylation450 BeadChip.</p< <p<Results</p< <p<Thirteen single nucleotide polymorphisms (SNPs) and twelve CpG sites of <it<IL4R</it< gene were analyzed. Based on linkage disequilibrium and association with asthma, eight SNPs and one CpG site were selected for further analyses. Of the twelve CpG sites in the <it<IL4R</it< gene, only methylation levels of cg09791102 showed an association with asthma at age 18 years (Wilcoxon test: <it<P</it< = 0.01). Log-linear models were used to estimate risk ratios (RRs) for asthma adjusting for uncorrelated SNPs within the <it<IL4R</it< gene and covariates. Testing for interaction between the eight SNPs and the methylation levels of cg09791102 on the risk for asthma at age 18 years, we identified the statistically significant interaction term of SNP rs3024685 × methylation levels of cg09791102 (<it<P</it< = 0.002; after adjusting for false discovery rate). A total of 84 participants had methylation levels ≤0.88, 112 participants between 0.89 and 0.90, and 35 between 0.91 and 0.92. For the SNP rs3024685 (‘CC’ vs. ‘TT’) at methylation levels of ≤0.85, 0.86, 0.90, 0.91, and 0.92, the RRs were 0.01, 0.04, 4.65, 14.76, 14.90, respectively (interaction effect, <it<P</it< = 0.0003).</p< <p<Conclusions</p< <p<Adjusting for multiple testing, our results suggest that DNA-M modulates the risk of asthma related to genetic variants in the <it<IL4R</it< gene. The strong interaction of one SNP and DNA-M is encouraging and provides a novel model of how a joint effect of genetic variants and DNA-M can explain occurrence of asthma.</p< Interleukin-4 receptor gene DNA methylation Genetic variants Asthma Epigenetics Medicine R Genetics Arshad Syed Hasan verfasserin aut Holloway John W verfasserin aut Zhang Hongmei verfasserin aut Schauberger Eric verfasserin aut Ewart Susan verfasserin aut Patil Veeresh verfasserin aut Karmaus Wilfried verfasserin aut In Clinical Epigenetics BMC, 2012 5(2013), 1, p 1 (DE-627)626459028 (DE-600)2553921-8 18687083 nnns volume:5 year:2013 number:1, p 1 https://doi.org/10.1186/1868-7083-5-1 kostenfrei https://doaj.org/article/b21d793ebb8a49ea9da9c8ee5d160f37 kostenfrei http://www.clinicalepigeneticsjournal.com/content/5/1/1 kostenfrei https://doaj.org/toc/1868-7083 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 5 2013 1, p 1
allfieldsSound	10.1186/1868-7083-5-1 doi (DE-627)DOAJ064994058 (DE-599)DOAJb21d793ebb8a49ea9da9c8ee5d160f37 DE-627 ger DE-627 rakwb eng QH426-470 Soto-Ramírez Nelís verfasserin aut The interaction of genetic variants and DNA methylation of the interleukin-4 receptor gene increase the risk of asthma at age 18 years 2013 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier <p<Abstract</p< <p<Background</p< <p<The occurrence of asthma is weakly explained by known genetic variants. Epigenetic marks, DNA methylation (DNA-M) in particular, are considered to add to the explanation of asthma. However, no etiological model has yet been developed that integrates genetic variants and DNA-M. To explore a new model, we focused on one asthma candidate gene, the IL-4 receptor (<it<IL4R</it<). We hypothesized that genetic variants of <it<IL4R</it< in interaction with DNA-M at cytosine-phosphate-guanine (CpG) sites jointly alter the risk of asthma during adolescence. Blood samples were collected at age 18 years from 245 female cohort participants randomly selected for methylation analysis from a birth cohort (n = 1,456, Isle of Wight, UK). Genome-wide DNA-M was assessed using the Illumina Infinium HumanMethylation450 BeadChip.</p< <p<Results</p< <p<Thirteen single nucleotide polymorphisms (SNPs) and twelve CpG sites of <it<IL4R</it< gene were analyzed. Based on linkage disequilibrium and association with asthma, eight SNPs and one CpG site were selected for further analyses. Of the twelve CpG sites in the <it<IL4R</it< gene, only methylation levels of cg09791102 showed an association with asthma at age 18 years (Wilcoxon test: <it<P</it< = 0.01). Log-linear models were used to estimate risk ratios (RRs) for asthma adjusting for uncorrelated SNPs within the <it<IL4R</it< gene and covariates. Testing for interaction between the eight SNPs and the methylation levels of cg09791102 on the risk for asthma at age 18 years, we identified the statistically significant interaction term of SNP rs3024685 × methylation levels of cg09791102 (<it<P</it< = 0.002; after adjusting for false discovery rate). A total of 84 participants had methylation levels ≤0.88, 112 participants between 0.89 and 0.90, and 35 between 0.91 and 0.92. For the SNP rs3024685 (‘CC’ vs. ‘TT’) at methylation levels of ≤0.85, 0.86, 0.90, 0.91, and 0.92, the RRs were 0.01, 0.04, 4.65, 14.76, 14.90, respectively (interaction effect, <it<P</it< = 0.0003).</p< <p<Conclusions</p< <p<Adjusting for multiple testing, our results suggest that DNA-M modulates the risk of asthma related to genetic variants in the <it<IL4R</it< gene. The strong interaction of one SNP and DNA-M is encouraging and provides a novel model of how a joint effect of genetic variants and DNA-M can explain occurrence of asthma.</p< Interleukin-4 receptor gene DNA methylation Genetic variants Asthma Epigenetics Medicine R Genetics Arshad Syed Hasan verfasserin aut Holloway John W verfasserin aut Zhang Hongmei verfasserin aut Schauberger Eric verfasserin aut Ewart Susan verfasserin aut Patil Veeresh verfasserin aut Karmaus Wilfried verfasserin aut In Clinical Epigenetics BMC, 2012 5(2013), 1, p 1 (DE-627)626459028 (DE-600)2553921-8 18687083 nnns volume:5 year:2013 number:1, p 1 https://doi.org/10.1186/1868-7083-5-1 kostenfrei https://doaj.org/article/b21d793ebb8a49ea9da9c8ee5d160f37 kostenfrei http://www.clinicalepigeneticsjournal.com/content/5/1/1 kostenfrei https://doaj.org/toc/1868-7083 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 5 2013 1, p 1
language	English
source	In Clinical Epigenetics 5(2013), 1, p 1 volume:5 year:2013 number:1, p 1
sourceStr	In Clinical Epigenetics 5(2013), 1, p 1 volume:5 year:2013 number:1, p 1
format_phy_str_mv	Article
institution	findex.gbv.de
topic_facet	Interleukin-4 receptor gene DNA methylation Genetic variants Asthma Epigenetics Medicine R Genetics
isfreeaccess_bool	true
container_title	Clinical Epigenetics
authorswithroles_txt_mv	Soto-Ramírez Nelís @@aut@@ Arshad Syed Hasan @@aut@@ Holloway John W @@aut@@ Zhang Hongmei @@aut@@ Schauberger Eric @@aut@@ Ewart Susan @@aut@@ Patil Veeresh @@aut@@ Karmaus Wilfried @@aut@@
publishDateDaySort_date	2013-01-01T00:00:00Z
hierarchy_top_id	626459028
id	DOAJ064994058
language_de	englisch
fullrecord	<?xml version="1.0" encoding="UTF-8"?><collection xmlns="http://www.loc.gov/MARC21/slim"><record><leader>01000caa a22002652 4500</leader><controlfield tag="001">DOAJ064994058</controlfield><controlfield tag="003">DE-627</controlfield><controlfield tag="005">20230309043718.0</controlfield><controlfield tag="007">cr uuu---uuuuu</controlfield><controlfield tag="008">230228s2013 xx \|\|\|\|\|o 00\| \|\|eng c</controlfield><datafield tag="024" ind1="7" ind2=" "><subfield code="a">10.1186/1868-7083-5-1</subfield><subfield code="2">doi</subfield></datafield><datafield tag="035" ind1=" " ind2=" "><subfield code="a">(DE-627)DOAJ064994058</subfield></datafield><datafield tag="035" ind1=" " ind2=" "><subfield code="a">(DE-599)DOAJb21d793ebb8a49ea9da9c8ee5d160f37</subfield></datafield><datafield tag="040" ind1=" " ind2=" "><subfield code="a">DE-627</subfield><subfield code="b">ger</subfield><subfield code="c">DE-627</subfield><subfield code="e">rakwb</subfield></datafield><datafield tag="041" ind1=" " ind2=" "><subfield code="a">eng</subfield></datafield><datafield tag="050" ind1=" " ind2="0"><subfield code="a">QH426-470</subfield></datafield><datafield tag="100" ind1="0" ind2=" "><subfield code="a">Soto-Ramírez Nelís</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="245" ind1="1" ind2="4"><subfield code="a">The interaction of genetic variants and DNA methylation of the interleukin-4 receptor gene increase the risk of asthma at age 18 years</subfield></datafield><datafield tag="264" ind1=" " ind2="1"><subfield code="c">2013</subfield></datafield><datafield tag="336" ind1=" " ind2=" "><subfield code="a">Text</subfield><subfield code="b">txt</subfield><subfield code="2">rdacontent</subfield></datafield><datafield tag="337" ind1=" " ind2=" "><subfield code="a">Computermedien</subfield><subfield code="b">c</subfield><subfield code="2">rdamedia</subfield></datafield><datafield tag="338" ind1=" " ind2=" "><subfield code="a">Online-Ressource</subfield><subfield code="b">cr</subfield><subfield code="2">rdacarrier</subfield></datafield><datafield tag="520" ind1=" " ind2=" "><subfield code="a"><p<Abstract</p< <p<Background</p< <p<The occurrence of asthma is weakly explained by known genetic variants. Epigenetic marks, DNA methylation (DNA-M) in particular, are considered to add to the explanation of asthma. However, no etiological model has yet been developed that integrates genetic variants and DNA-M. To explore a new model, we focused on one asthma candidate gene, the IL-4 receptor (<it<IL4R</it<). We hypothesized that genetic variants of <it<IL4R</it< in interaction with DNA-M at cytosine-phosphate-guanine (CpG) sites jointly alter the risk of asthma during adolescence. Blood samples were collected at age 18 years from 245 female cohort participants randomly selected for methylation analysis from a birth cohort (n = 1,456, Isle of Wight, UK). Genome-wide DNA-M was assessed using the Illumina Infinium HumanMethylation450 BeadChip.</p< <p<Results</p< <p<Thirteen single nucleotide polymorphisms (SNPs) and twelve CpG sites of <it<IL4R</it< gene were analyzed. Based on linkage disequilibrium and association with asthma, eight SNPs and one CpG site were selected for further analyses. Of the twelve CpG sites in the <it<IL4R</it< gene, only methylation levels of cg09791102 showed an association with asthma at age 18 years (Wilcoxon test: <it<P</it< = 0.01). Log-linear models were used to estimate risk ratios (RRs) for asthma adjusting for uncorrelated SNPs within the <it<IL4R</it< gene and covariates. Testing for interaction between the eight SNPs and the methylation levels of cg09791102 on the risk for asthma at age 18 years, we identified the statistically significant interaction term of SNP rs3024685 × methylation levels of cg09791102 (<it<P</it< = 0.002; after adjusting for false discovery rate). A total of 84 participants had methylation levels ≤0.88, 112 participants between 0.89 and 0.90, and 35 between 0.91 and 0.92. For the SNP rs3024685 (‘CC’ vs. ‘TT’) at methylation levels of ≤0.85, 0.86, 0.90, 0.91, and 0.92, the RRs were 0.01, 0.04, 4.65, 14.76, 14.90, respectively (interaction effect, <it<P</it< = 0.0003).</p< <p<Conclusions</p< <p<Adjusting for multiple testing, our results suggest that DNA-M modulates the risk of asthma related to genetic variants in the <it<IL4R</it< gene. The strong interaction of one SNP and DNA-M is encouraging and provides a novel model of how a joint effect of genetic variants and DNA-M can explain occurrence of asthma.</p<</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Interleukin-4 receptor gene</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">DNA methylation</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Genetic variants</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Asthma</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Epigenetics</subfield></datafield><datafield tag="653" ind1=" " ind2="0"><subfield code="a">Medicine</subfield></datafield><datafield tag="653" ind1=" " ind2="0"><subfield code="a">R</subfield></datafield><datafield tag="653" ind1=" " ind2="0"><subfield code="a">Genetics</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield 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callnumber-first	Q - Science
author	Soto-Ramírez Nelís
spellingShingle	Soto-Ramírez Nelís misc QH426-470 misc Interleukin-4 receptor gene misc DNA methylation misc Genetic variants misc Asthma misc Epigenetics misc Medicine misc R misc Genetics The interaction of genetic variants and DNA methylation of the interleukin-4 receptor gene increase the risk of asthma at age 18 years
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topic_title	QH426-470 The interaction of genetic variants and DNA methylation of the interleukin-4 receptor gene increase the risk of asthma at age 18 years Interleukin-4 receptor gene DNA methylation Genetic variants Asthma Epigenetics
topic	misc QH426-470 misc Interleukin-4 receptor gene misc DNA methylation misc Genetic variants misc Asthma misc Epigenetics misc Medicine misc R misc Genetics
topic_unstemmed	misc QH426-470 misc Interleukin-4 receptor gene misc DNA methylation misc Genetic variants misc Asthma misc Epigenetics misc Medicine misc R misc Genetics
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title	The interaction of genetic variants and DNA methylation of the interleukin-4 receptor gene increase the risk of asthma at age 18 years
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title_full	The interaction of genetic variants and DNA methylation of the interleukin-4 receptor gene increase the risk of asthma at age 18 years
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author_browse	Soto-Ramírez Nelís Arshad Syed Hasan Holloway John W Zhang Hongmei Schauberger Eric Ewart Susan Patil Veeresh Karmaus Wilfried
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title_sort	interaction of genetic variants and dna methylation of the interleukin-4 receptor gene increase the risk of asthma at age 18 years
callnumber	QH426-470
title_auth	The interaction of genetic variants and DNA methylation of the interleukin-4 receptor gene increase the risk of asthma at age 18 years
abstract	<p<Abstract</p< <p<Background</p< <p<The occurrence of asthma is weakly explained by known genetic variants. Epigenetic marks, DNA methylation (DNA-M) in particular, are considered to add to the explanation of asthma. However, no etiological model has yet been developed that integrates genetic variants and DNA-M. To explore a new model, we focused on one asthma candidate gene, the IL-4 receptor (<it<IL4R</it<). We hypothesized that genetic variants of <it<IL4R</it< in interaction with DNA-M at cytosine-phosphate-guanine (CpG) sites jointly alter the risk of asthma during adolescence. Blood samples were collected at age 18 years from 245 female cohort participants randomly selected for methylation analysis from a birth cohort (n = 1,456, Isle of Wight, UK). Genome-wide DNA-M was assessed using the Illumina Infinium HumanMethylation450 BeadChip.</p< <p<Results</p< <p<Thirteen single nucleotide polymorphisms (SNPs) and twelve CpG sites of <it<IL4R</it< gene were analyzed. Based on linkage disequilibrium and association with asthma, eight SNPs and one CpG site were selected for further analyses. Of the twelve CpG sites in the <it<IL4R</it< gene, only methylation levels of cg09791102 showed an association with asthma at age 18 years (Wilcoxon test: <it<P</it< = 0.01). Log-linear models were used to estimate risk ratios (RRs) for asthma adjusting for uncorrelated SNPs within the <it<IL4R</it< gene and covariates. Testing for interaction between the eight SNPs and the methylation levels of cg09791102 on the risk for asthma at age 18 years, we identified the statistically significant interaction term of SNP rs3024685 × methylation levels of cg09791102 (<it<P</it< = 0.002; after adjusting for false discovery rate). A total of 84 participants had methylation levels ≤0.88, 112 participants between 0.89 and 0.90, and 35 between 0.91 and 0.92. For the SNP rs3024685 (‘CC’ vs. ‘TT’) at methylation levels of ≤0.85, 0.86, 0.90, 0.91, and 0.92, the RRs were 0.01, 0.04, 4.65, 14.76, 14.90, respectively (interaction effect, <it<P</it< = 0.0003).</p< <p<Conclusions</p< <p<Adjusting for multiple testing, our results suggest that DNA-M modulates the risk of asthma related to genetic variants in the <it<IL4R</it< gene. The strong interaction of one SNP and DNA-M is encouraging and provides a novel model of how a joint effect of genetic variants and DNA-M can explain occurrence of asthma.</p<
abstractGer	<p<Abstract</p< <p<Background</p< <p<The occurrence of asthma is weakly explained by known genetic variants. Epigenetic marks, DNA methylation (DNA-M) in particular, are considered to add to the explanation of asthma. However, no etiological model has yet been developed that integrates genetic variants and DNA-M. To explore a new model, we focused on one asthma candidate gene, the IL-4 receptor (<it<IL4R</it<). We hypothesized that genetic variants of <it<IL4R</it< in interaction with DNA-M at cytosine-phosphate-guanine (CpG) sites jointly alter the risk of asthma during adolescence. Blood samples were collected at age 18 years from 245 female cohort participants randomly selected for methylation analysis from a birth cohort (n = 1,456, Isle of Wight, UK). Genome-wide DNA-M was assessed using the Illumina Infinium HumanMethylation450 BeadChip.</p< <p<Results</p< <p<Thirteen single nucleotide polymorphisms (SNPs) and twelve CpG sites of <it<IL4R</it< gene were analyzed. Based on linkage disequilibrium and association with asthma, eight SNPs and one CpG site were selected for further analyses. Of the twelve CpG sites in the <it<IL4R</it< gene, only methylation levels of cg09791102 showed an association with asthma at age 18 years (Wilcoxon test: <it<P</it< = 0.01). Log-linear models were used to estimate risk ratios (RRs) for asthma adjusting for uncorrelated SNPs within the <it<IL4R</it< gene and covariates. Testing for interaction between the eight SNPs and the methylation levels of cg09791102 on the risk for asthma at age 18 years, we identified the statistically significant interaction term of SNP rs3024685 × methylation levels of cg09791102 (<it<P</it< = 0.002; after adjusting for false discovery rate). A total of 84 participants had methylation levels ≤0.88, 112 participants between 0.89 and 0.90, and 35 between 0.91 and 0.92. For the SNP rs3024685 (‘CC’ vs. ‘TT’) at methylation levels of ≤0.85, 0.86, 0.90, 0.91, and 0.92, the RRs were 0.01, 0.04, 4.65, 14.76, 14.90, respectively (interaction effect, <it<P</it< = 0.0003).</p< <p<Conclusions</p< <p<Adjusting for multiple testing, our results suggest that DNA-M modulates the risk of asthma related to genetic variants in the <it<IL4R</it< gene. The strong interaction of one SNP and DNA-M is encouraging and provides a novel model of how a joint effect of genetic variants and DNA-M can explain occurrence of asthma.</p<
abstract_unstemmed	<p<Abstract</p< <p<Background</p< <p<The occurrence of asthma is weakly explained by known genetic variants. Epigenetic marks, DNA methylation (DNA-M) in particular, are considered to add to the explanation of asthma. However, no etiological model has yet been developed that integrates genetic variants and DNA-M. To explore a new model, we focused on one asthma candidate gene, the IL-4 receptor (<it<IL4R</it<). We hypothesized that genetic variants of <it<IL4R</it< in interaction with DNA-M at cytosine-phosphate-guanine (CpG) sites jointly alter the risk of asthma during adolescence. Blood samples were collected at age 18 years from 245 female cohort participants randomly selected for methylation analysis from a birth cohort (n = 1,456, Isle of Wight, UK). Genome-wide DNA-M was assessed using the Illumina Infinium HumanMethylation450 BeadChip.</p< <p<Results</p< <p<Thirteen single nucleotide polymorphisms (SNPs) and twelve CpG sites of <it<IL4R</it< gene were analyzed. Based on linkage disequilibrium and association with asthma, eight SNPs and one CpG site were selected for further analyses. Of the twelve CpG sites in the <it<IL4R</it< gene, only methylation levels of cg09791102 showed an association with asthma at age 18 years (Wilcoxon test: <it<P</it< = 0.01). Log-linear models were used to estimate risk ratios (RRs) for asthma adjusting for uncorrelated SNPs within the <it<IL4R</it< gene and covariates. Testing for interaction between the eight SNPs and the methylation levels of cg09791102 on the risk for asthma at age 18 years, we identified the statistically significant interaction term of SNP rs3024685 × methylation levels of cg09791102 (<it<P</it< = 0.002; after adjusting for false discovery rate). A total of 84 participants had methylation levels ≤0.88, 112 participants between 0.89 and 0.90, and 35 between 0.91 and 0.92. For the SNP rs3024685 (‘CC’ vs. ‘TT’) at methylation levels of ≤0.85, 0.86, 0.90, 0.91, and 0.92, the RRs were 0.01, 0.04, 4.65, 14.76, 14.90, respectively (interaction effect, <it<P</it< = 0.0003).</p< <p<Conclusions</p< <p<Adjusting for multiple testing, our results suggest that DNA-M modulates the risk of asthma related to genetic variants in the <it<IL4R</it< gene. The strong interaction of one SNP and DNA-M is encouraging and provides a novel model of how a joint effect of genetic variants and DNA-M can explain occurrence of asthma.</p<
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title_short	The interaction of genetic variants and DNA methylation of the interleukin-4 receptor gene increase the risk of asthma at age 18 years
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For the SNP rs3024685 (‘CC’ vs. ‘TT’) at methylation levels of ≤0.85, 0.86, 0.90, 0.91, and 0.92, the RRs were 0.01, 0.04, 4.65, 14.76, 14.90, respectively (interaction effect, <it<P</it< = 0.0003).</p< <p<Conclusions</p< <p<Adjusting for multiple testing, our results suggest that DNA-M modulates the risk of asthma related to genetic variants in the <it<IL4R</it< gene. 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The interaction of genetic variants and DNA methylation of the interleukin-4 receptor gene increase the risk of asthma at age 18 years

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