The interplay of DNA methylation over time with Th2 pathway genetic variants on asthma risk and temporal asthma transition

Background Genetic effects on asthma of genes in the T-helper 2 (Th2) pathway may interact with epigenetic factors including DNA methylation. We hypothesized that interactions between genetic variants and methylation in genes in this pathway (IL4, IL4R, IL13, GATA3, and STAT6) influence asthma risk, that such influences are age-dependent, and that methylation of some CpG sites changes over time in accordance with asthma transition. We tested these hypotheses in subsamples of girls from a population-based birth cohort established on the Isle of Wight, UK, in 1989. Results Logistic regression models were applied to test the interaction effect of DNA methylation and SNP on asthma within each of the five genes. Bootstrapping was used to assess the models identified. From 1,361 models fitted at each age of 10 and 18 years, 8 models, including 4 CpGs and 8 SNPs, showed potential associations with asthma risk. Of the 4 CpGs, methylation of cg26937798 (IL4R) and cg23943829 (IL4) changes between ages 10 and 18 (both higher at 10; P = 9.14 × $ 10^{−6} $ and 1.07 × $ 10^{−5} $, respectively). At age 10, the odds of asthma tended to decrease as cg12405139 (GATA3) methylation increased (log-OR = −12.15; P = 0.049); this effect disappeared by age 18. At age 18, methylation of cg09791102 (IL4R) was associated with higher risk of asthma among subjects with genotype GG compared to AG (P = 0.003), increased cg26937798 methylation among subjects with rs3024685 (IL4R) genotype AA (P = 0.003) or rs8832 (IL4R) genotype GG (P = 0.01) was associated with a lower asthma risk; these CpGs had no effect at age 10. Increasing cg26937798 methylation over time possibly reduced the risk of positive asthma transition (asthma-free at age 10 → asthma at age 18; log-OR = −3.11; P = 0.069) and increased the likelihood of negative transition (asthma at age 10 → asthma-free at age 18; log-OR = 3.97; P = 0.074). Conclusions The interaction of DNA methylation and SNPs in Th2 pathway genes is likely to contribute to asthma risk. This effect may vary with age. Methylation of some CpGs changed over time, which may influence asthma transition. Ausführliche Beschreibung

Gespeichert in:

Autor*in:	Zhang, Hongmei [verfasserIn] Tong, Xin Holloway, John W Rezwan, Faisal I Lockett, Gabrielle A Patil, Veeresh Ray, Meredith Everson, Todd M Soto-Ramírez, Nelís Arshad, S Hasan Ewart, Susan Karmaus, Wilfried

Format:	E-Artikel
Sprache:	Englisch

Erschienen:	2014

Schlagwörter:	Asthma risk Asthma transition DNA methylation and SNP interaction Th2 pathway

Anmerkung:	© Zhang et al.; licensee BioMed Central Ltd. 2014

Übergeordnetes Werk:	Enthalten in: Clinical epigenetics - [S.l.] : BioMed Central, 2010, 6(2014), 1 vom: 15. Apr.
Übergeordnetes Werk:	volume:6 ; year:2014 ; number:1 ; day:15 ; month:04

Links:	Volltext

DOI / URN:	10.1186/1868-7083-6-8

Katalog-ID:	SPR030671140

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520			\|a Background Genetic effects on asthma of genes in the T-helper 2 (Th2) pathway may interact with epigenetic factors including DNA methylation. We hypothesized that interactions between genetic variants and methylation in genes in this pathway (IL4, IL4R, IL13, GATA3, and STAT6) influence asthma risk, that such influences are age-dependent, and that methylation of some CpG sites changes over time in accordance with asthma transition. We tested these hypotheses in subsamples of girls from a population-based birth cohort established on the Isle of Wight, UK, in 1989. Results Logistic regression models were applied to test the interaction effect of DNA methylation and SNP on asthma within each of the five genes. Bootstrapping was used to assess the models identified. From 1,361 models fitted at each age of 10 and 18 years, 8 models, including 4 CpGs and 8 SNPs, showed potential associations with asthma risk. Of the 4 CpGs, methylation of cg26937798 (IL4R) and cg23943829 (IL4) changes between ages 10 and 18 (both higher at 10; P = 9.14 × $ 10^{−6} $ and 1.07 × $ 10^{−5} $, respectively). At age 10, the odds of asthma tended to decrease as cg12405139 (GATA3) methylation increased (log-OR = −12.15; P = 0.049); this effect disappeared by age 18. At age 18, methylation of cg09791102 (IL4R) was associated with higher risk of asthma among subjects with genotype GG compared to AG (P = 0.003), increased cg26937798 methylation among subjects with rs3024685 (IL4R) genotype AA (P = 0.003) or rs8832 (IL4R) genotype GG (P = 0.01) was associated with a lower asthma risk; these CpGs had no effect at age 10. Increasing cg26937798 methylation over time possibly reduced the risk of positive asthma transition (asthma-free at age 10 → asthma at age 18; log-OR = −3.11; P = 0.069) and increased the likelihood of negative transition (asthma at age 10 → asthma-free at age 18; log-OR = 3.97; P = 0.074). Conclusions The interaction of DNA methylation and SNPs in Th2 pathway genes is likely to contribute to asthma risk. This effect may vary with age. Methylation of some CpGs changed over time, which may influence asthma transition.
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allfields	10.1186/1868-7083-6-8 doi (DE-627)SPR030671140 (SPR)1868-7083-6-8-e DE-627 ger DE-627 rakwb eng Zhang, Hongmei verfasserin aut The interplay of DNA methylation over time with Th2 pathway genetic variants on asthma risk and temporal asthma transition 2014 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © Zhang et al.; licensee BioMed Central Ltd. 2014 Background Genetic effects on asthma of genes in the T-helper 2 (Th2) pathway may interact with epigenetic factors including DNA methylation. We hypothesized that interactions between genetic variants and methylation in genes in this pathway (IL4, IL4R, IL13, GATA3, and STAT6) influence asthma risk, that such influences are age-dependent, and that methylation of some CpG sites changes over time in accordance with asthma transition. We tested these hypotheses in subsamples of girls from a population-based birth cohort established on the Isle of Wight, UK, in 1989. Results Logistic regression models were applied to test the interaction effect of DNA methylation and SNP on asthma within each of the five genes. Bootstrapping was used to assess the models identified. From 1,361 models fitted at each age of 10 and 18 years, 8 models, including 4 CpGs and 8 SNPs, showed potential associations with asthma risk. Of the 4 CpGs, methylation of cg26937798 (IL4R) and cg23943829 (IL4) changes between ages 10 and 18 (both higher at 10; P = 9.14 × $ 10^{−6} $ and 1.07 × $ 10^{−5} $, respectively). At age 10, the odds of asthma tended to decrease as cg12405139 (GATA3) methylation increased (log-OR = −12.15; P = 0.049); this effect disappeared by age 18. At age 18, methylation of cg09791102 (IL4R) was associated with higher risk of asthma among subjects with genotype GG compared to AG (P = 0.003), increased cg26937798 methylation among subjects with rs3024685 (IL4R) genotype AA (P = 0.003) or rs8832 (IL4R) genotype GG (P = 0.01) was associated with a lower asthma risk; these CpGs had no effect at age 10. Increasing cg26937798 methylation over time possibly reduced the risk of positive asthma transition (asthma-free at age 10 → asthma at age 18; log-OR = −3.11; P = 0.069) and increased the likelihood of negative transition (asthma at age 10 → asthma-free at age 18; log-OR = 3.97; P = 0.074). Conclusions The interaction of DNA methylation and SNPs in Th2 pathway genes is likely to contribute to asthma risk. This effect may vary with age. Methylation of some CpGs changed over time, which may influence asthma transition. Asthma risk (dpeaa)DE-He213 Asthma transition (dpeaa)DE-He213 DNA methylation and SNP interaction (dpeaa)DE-He213 Th2 pathway (dpeaa)DE-He213 Tong, Xin aut Holloway, John W aut Rezwan, Faisal I aut Lockett, Gabrielle A aut Patil, Veeresh aut Ray, Meredith aut Everson, Todd M aut Soto-Ramírez, Nelís aut Arshad, S Hasan aut Ewart, Susan aut Karmaus, Wilfried aut Enthalten in Clinical epigenetics [S.l.] : BioMed Central, 2010 6(2014), 1 vom: 15. Apr. (DE-627)626459028 (DE-600)2553921-8 1868-7083 nnns volume:6 year:2014 number:1 day:15 month:04 https://dx.doi.org/10.1186/1868-7083-6-8 kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA 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 6 2014 1 15 04
spelling	10.1186/1868-7083-6-8 doi (DE-627)SPR030671140 (SPR)1868-7083-6-8-e DE-627 ger DE-627 rakwb eng Zhang, Hongmei verfasserin aut The interplay of DNA methylation over time with Th2 pathway genetic variants on asthma risk and temporal asthma transition 2014 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © Zhang et al.; licensee BioMed Central Ltd. 2014 Background Genetic effects on asthma of genes in the T-helper 2 (Th2) pathway may interact with epigenetic factors including DNA methylation. We hypothesized that interactions between genetic variants and methylation in genes in this pathway (IL4, IL4R, IL13, GATA3, and STAT6) influence asthma risk, that such influences are age-dependent, and that methylation of some CpG sites changes over time in accordance with asthma transition. We tested these hypotheses in subsamples of girls from a population-based birth cohort established on the Isle of Wight, UK, in 1989. Results Logistic regression models were applied to test the interaction effect of DNA methylation and SNP on asthma within each of the five genes. Bootstrapping was used to assess the models identified. From 1,361 models fitted at each age of 10 and 18 years, 8 models, including 4 CpGs and 8 SNPs, showed potential associations with asthma risk. Of the 4 CpGs, methylation of cg26937798 (IL4R) and cg23943829 (IL4) changes between ages 10 and 18 (both higher at 10; P = 9.14 × $ 10^{−6} $ and 1.07 × $ 10^{−5} $, respectively). At age 10, the odds of asthma tended to decrease as cg12405139 (GATA3) methylation increased (log-OR = −12.15; P = 0.049); this effect disappeared by age 18. At age 18, methylation of cg09791102 (IL4R) was associated with higher risk of asthma among subjects with genotype GG compared to AG (P = 0.003), increased cg26937798 methylation among subjects with rs3024685 (IL4R) genotype AA (P = 0.003) or rs8832 (IL4R) genotype GG (P = 0.01) was associated with a lower asthma risk; these CpGs had no effect at age 10. Increasing cg26937798 methylation over time possibly reduced the risk of positive asthma transition (asthma-free at age 10 → asthma at age 18; log-OR = −3.11; P = 0.069) and increased the likelihood of negative transition (asthma at age 10 → asthma-free at age 18; log-OR = 3.97; P = 0.074). Conclusions The interaction of DNA methylation and SNPs in Th2 pathway genes is likely to contribute to asthma risk. This effect may vary with age. Methylation of some CpGs changed over time, which may influence asthma transition. Asthma risk (dpeaa)DE-He213 Asthma transition (dpeaa)DE-He213 DNA methylation and SNP interaction (dpeaa)DE-He213 Th2 pathway (dpeaa)DE-He213 Tong, Xin aut Holloway, John W aut Rezwan, Faisal I aut Lockett, Gabrielle A aut Patil, Veeresh aut Ray, Meredith aut Everson, Todd M aut Soto-Ramírez, Nelís aut Arshad, S Hasan aut Ewart, Susan aut Karmaus, Wilfried aut Enthalten in Clinical epigenetics [S.l.] : BioMed Central, 2010 6(2014), 1 vom: 15. Apr. (DE-627)626459028 (DE-600)2553921-8 1868-7083 nnns volume:6 year:2014 number:1 day:15 month:04 https://dx.doi.org/10.1186/1868-7083-6-8 kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA 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 6 2014 1 15 04
allfields_unstemmed	10.1186/1868-7083-6-8 doi (DE-627)SPR030671140 (SPR)1868-7083-6-8-e DE-627 ger DE-627 rakwb eng Zhang, Hongmei verfasserin aut The interplay of DNA methylation over time with Th2 pathway genetic variants on asthma risk and temporal asthma transition 2014 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © Zhang et al.; licensee BioMed Central Ltd. 2014 Background Genetic effects on asthma of genes in the T-helper 2 (Th2) pathway may interact with epigenetic factors including DNA methylation. We hypothesized that interactions between genetic variants and methylation in genes in this pathway (IL4, IL4R, IL13, GATA3, and STAT6) influence asthma risk, that such influences are age-dependent, and that methylation of some CpG sites changes over time in accordance with asthma transition. We tested these hypotheses in subsamples of girls from a population-based birth cohort established on the Isle of Wight, UK, in 1989. Results Logistic regression models were applied to test the interaction effect of DNA methylation and SNP on asthma within each of the five genes. Bootstrapping was used to assess the models identified. From 1,361 models fitted at each age of 10 and 18 years, 8 models, including 4 CpGs and 8 SNPs, showed potential associations with asthma risk. Of the 4 CpGs, methylation of cg26937798 (IL4R) and cg23943829 (IL4) changes between ages 10 and 18 (both higher at 10; P = 9.14 × $ 10^{−6} $ and 1.07 × $ 10^{−5} $, respectively). At age 10, the odds of asthma tended to decrease as cg12405139 (GATA3) methylation increased (log-OR = −12.15; P = 0.049); this effect disappeared by age 18. At age 18, methylation of cg09791102 (IL4R) was associated with higher risk of asthma among subjects with genotype GG compared to AG (P = 0.003), increased cg26937798 methylation among subjects with rs3024685 (IL4R) genotype AA (P = 0.003) or rs8832 (IL4R) genotype GG (P = 0.01) was associated with a lower asthma risk; these CpGs had no effect at age 10. Increasing cg26937798 methylation over time possibly reduced the risk of positive asthma transition (asthma-free at age 10 → asthma at age 18; log-OR = −3.11; P = 0.069) and increased the likelihood of negative transition (asthma at age 10 → asthma-free at age 18; log-OR = 3.97; P = 0.074). Conclusions The interaction of DNA methylation and SNPs in Th2 pathway genes is likely to contribute to asthma risk. This effect may vary with age. Methylation of some CpGs changed over time, which may influence asthma transition. Asthma risk (dpeaa)DE-He213 Asthma transition (dpeaa)DE-He213 DNA methylation and SNP interaction (dpeaa)DE-He213 Th2 pathway (dpeaa)DE-He213 Tong, Xin aut Holloway, John W aut Rezwan, Faisal I aut Lockett, Gabrielle A aut Patil, Veeresh aut Ray, Meredith aut Everson, Todd M aut Soto-Ramírez, Nelís aut Arshad, S Hasan aut Ewart, Susan aut Karmaus, Wilfried aut Enthalten in Clinical epigenetics [S.l.] : BioMed Central, 2010 6(2014), 1 vom: 15. Apr. (DE-627)626459028 (DE-600)2553921-8 1868-7083 nnns volume:6 year:2014 number:1 day:15 month:04 https://dx.doi.org/10.1186/1868-7083-6-8 kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA 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 6 2014 1 15 04
allfieldsGer	10.1186/1868-7083-6-8 doi (DE-627)SPR030671140 (SPR)1868-7083-6-8-e DE-627 ger DE-627 rakwb eng Zhang, Hongmei verfasserin aut The interplay of DNA methylation over time with Th2 pathway genetic variants on asthma risk and temporal asthma transition 2014 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © Zhang et al.; licensee BioMed Central Ltd. 2014 Background Genetic effects on asthma of genes in the T-helper 2 (Th2) pathway may interact with epigenetic factors including DNA methylation. We hypothesized that interactions between genetic variants and methylation in genes in this pathway (IL4, IL4R, IL13, GATA3, and STAT6) influence asthma risk, that such influences are age-dependent, and that methylation of some CpG sites changes over time in accordance with asthma transition. We tested these hypotheses in subsamples of girls from a population-based birth cohort established on the Isle of Wight, UK, in 1989. Results Logistic regression models were applied to test the interaction effect of DNA methylation and SNP on asthma within each of the five genes. Bootstrapping was used to assess the models identified. From 1,361 models fitted at each age of 10 and 18 years, 8 models, including 4 CpGs and 8 SNPs, showed potential associations with asthma risk. Of the 4 CpGs, methylation of cg26937798 (IL4R) and cg23943829 (IL4) changes between ages 10 and 18 (both higher at 10; P = 9.14 × $ 10^{−6} $ and 1.07 × $ 10^{−5} $, respectively). At age 10, the odds of asthma tended to decrease as cg12405139 (GATA3) methylation increased (log-OR = −12.15; P = 0.049); this effect disappeared by age 18. At age 18, methylation of cg09791102 (IL4R) was associated with higher risk of asthma among subjects with genotype GG compared to AG (P = 0.003), increased cg26937798 methylation among subjects with rs3024685 (IL4R) genotype AA (P = 0.003) or rs8832 (IL4R) genotype GG (P = 0.01) was associated with a lower asthma risk; these CpGs had no effect at age 10. Increasing cg26937798 methylation over time possibly reduced the risk of positive asthma transition (asthma-free at age 10 → asthma at age 18; log-OR = −3.11; P = 0.069) and increased the likelihood of negative transition (asthma at age 10 → asthma-free at age 18; log-OR = 3.97; P = 0.074). Conclusions The interaction of DNA methylation and SNPs in Th2 pathway genes is likely to contribute to asthma risk. This effect may vary with age. Methylation of some CpGs changed over time, which may influence asthma transition. Asthma risk (dpeaa)DE-He213 Asthma transition (dpeaa)DE-He213 DNA methylation and SNP interaction (dpeaa)DE-He213 Th2 pathway (dpeaa)DE-He213 Tong, Xin aut Holloway, John W aut Rezwan, Faisal I aut Lockett, Gabrielle A aut Patil, Veeresh aut Ray, Meredith aut Everson, Todd M aut Soto-Ramírez, Nelís aut Arshad, S Hasan aut Ewart, Susan aut Karmaus, Wilfried aut Enthalten in Clinical epigenetics [S.l.] : BioMed Central, 2010 6(2014), 1 vom: 15. Apr. (DE-627)626459028 (DE-600)2553921-8 1868-7083 nnns volume:6 year:2014 number:1 day:15 month:04 https://dx.doi.org/10.1186/1868-7083-6-8 kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA 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 6 2014 1 15 04
allfieldsSound	10.1186/1868-7083-6-8 doi (DE-627)SPR030671140 (SPR)1868-7083-6-8-e DE-627 ger DE-627 rakwb eng Zhang, Hongmei verfasserin aut The interplay of DNA methylation over time with Th2 pathway genetic variants on asthma risk and temporal asthma transition 2014 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © Zhang et al.; licensee BioMed Central Ltd. 2014 Background Genetic effects on asthma of genes in the T-helper 2 (Th2) pathway may interact with epigenetic factors including DNA methylation. We hypothesized that interactions between genetic variants and methylation in genes in this pathway (IL4, IL4R, IL13, GATA3, and STAT6) influence asthma risk, that such influences are age-dependent, and that methylation of some CpG sites changes over time in accordance with asthma transition. We tested these hypotheses in subsamples of girls from a population-based birth cohort established on the Isle of Wight, UK, in 1989. Results Logistic regression models were applied to test the interaction effect of DNA methylation and SNP on asthma within each of the five genes. Bootstrapping was used to assess the models identified. From 1,361 models fitted at each age of 10 and 18 years, 8 models, including 4 CpGs and 8 SNPs, showed potential associations with asthma risk. Of the 4 CpGs, methylation of cg26937798 (IL4R) and cg23943829 (IL4) changes between ages 10 and 18 (both higher at 10; P = 9.14 × $ 10^{−6} $ and 1.07 × $ 10^{−5} $, respectively). At age 10, the odds of asthma tended to decrease as cg12405139 (GATA3) methylation increased (log-OR = −12.15; P = 0.049); this effect disappeared by age 18. At age 18, methylation of cg09791102 (IL4R) was associated with higher risk of asthma among subjects with genotype GG compared to AG (P = 0.003), increased cg26937798 methylation among subjects with rs3024685 (IL4R) genotype AA (P = 0.003) or rs8832 (IL4R) genotype GG (P = 0.01) was associated with a lower asthma risk; these CpGs had no effect at age 10. Increasing cg26937798 methylation over time possibly reduced the risk of positive asthma transition (asthma-free at age 10 → asthma at age 18; log-OR = −3.11; P = 0.069) and increased the likelihood of negative transition (asthma at age 10 → asthma-free at age 18; log-OR = 3.97; P = 0.074). Conclusions The interaction of DNA methylation and SNPs in Th2 pathway genes is likely to contribute to asthma risk. This effect may vary with age. Methylation of some CpGs changed over time, which may influence asthma transition. Asthma risk (dpeaa)DE-He213 Asthma transition (dpeaa)DE-He213 DNA methylation and SNP interaction (dpeaa)DE-He213 Th2 pathway (dpeaa)DE-He213 Tong, Xin aut Holloway, John W aut Rezwan, Faisal I aut Lockett, Gabrielle A aut Patil, Veeresh aut Ray, Meredith aut Everson, Todd M aut Soto-Ramírez, Nelís aut Arshad, S Hasan aut Ewart, Susan aut Karmaus, Wilfried aut Enthalten in Clinical epigenetics [S.l.] : BioMed Central, 2010 6(2014), 1 vom: 15. Apr. (DE-627)626459028 (DE-600)2553921-8 1868-7083 nnns volume:6 year:2014 number:1 day:15 month:04 https://dx.doi.org/10.1186/1868-7083-6-8 kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA 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 6 2014 1 15 04
language	English
source	Enthalten in Clinical epigenetics 6(2014), 1 vom: 15. Apr. volume:6 year:2014 number:1 day:15 month:04
sourceStr	Enthalten in Clinical epigenetics 6(2014), 1 vom: 15. Apr. volume:6 year:2014 number:1 day:15 month:04
format_phy_str_mv	Article
institution	findex.gbv.de
topic_facet	Asthma risk Asthma transition DNA methylation and SNP interaction Th2 pathway
isfreeaccess_bool	true
container_title	Clinical epigenetics
authorswithroles_txt_mv	Zhang, Hongmei @@aut@@ Tong, Xin @@aut@@ Holloway, John W @@aut@@ Rezwan, Faisal I @@aut@@ Lockett, Gabrielle A @@aut@@ Patil, Veeresh @@aut@@ Ray, Meredith @@aut@@ Everson, Todd M @@aut@@ Soto-Ramírez, Nelís @@aut@@ Arshad, S Hasan @@aut@@ Ewart, Susan @@aut@@ Karmaus, Wilfried @@aut@@
publishDateDaySort_date	2014-04-15T00:00:00Z
hierarchy_top_id	626459028
id	SPR030671140
language_de	englisch
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We hypothesized that interactions between genetic variants and methylation in genes in this pathway (IL4, IL4R, IL13, GATA3, and STAT6) influence asthma risk, that such influences are age-dependent, and that methylation of some CpG sites changes over time in accordance with asthma transition. We tested these hypotheses in subsamples of girls from a population-based birth cohort established on the Isle of Wight, UK, in 1989. Results Logistic regression models were applied to test the interaction effect of DNA methylation and SNP on asthma within each of the five genes. Bootstrapping was used to assess the models identified. From 1,361 models fitted at each age of 10 and 18 years, 8 models, including 4 CpGs and 8 SNPs, showed potential associations with asthma risk. Of the 4 CpGs, methylation of cg26937798 (IL4R) and cg23943829 (IL4) changes between ages 10 and 18 (both higher at 10; P = 9.14 × $ 10^{−6} $ and 1.07 × $ 10^{−5} $, respectively). At age 10, the odds of asthma tended to decrease as cg12405139 (GATA3) methylation increased (log-OR = −12.15; P = 0.049); this effect disappeared by age 18. At age 18, methylation of cg09791102 (IL4R) was associated with higher risk of asthma among subjects with genotype GG compared to AG (P = 0.003), increased cg26937798 methylation among subjects with rs3024685 (IL4R) genotype AA (P = 0.003) or rs8832 (IL4R) genotype GG (P = 0.01) was associated with a lower asthma risk; these CpGs had no effect at age 10. Increasing cg26937798 methylation over time possibly reduced the risk of positive asthma transition (asthma-free at age 10 → asthma at age 18; log-OR = −3.11; P = 0.069) and increased the likelihood of negative transition (asthma at age 10 → asthma-free at age 18; log-OR = 3.97; P = 0.074). Conclusions The interaction of DNA methylation and SNPs in Th2 pathway genes is likely to contribute to asthma risk. This effect may vary with age. 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author	Zhang, Hongmei
spellingShingle	Zhang, Hongmei misc Asthma risk misc Asthma transition misc DNA methylation and SNP interaction misc Th2 pathway The interplay of DNA methylation over time with Th2 pathway genetic variants on asthma risk and temporal asthma transition
authorStr	Zhang, Hongmei
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topic_title	The interplay of DNA methylation over time with Th2 pathway genetic variants on asthma risk and temporal asthma transition Asthma risk (dpeaa)DE-He213 Asthma transition (dpeaa)DE-He213 DNA methylation and SNP interaction (dpeaa)DE-He213 Th2 pathway (dpeaa)DE-He213
topic	misc Asthma risk misc Asthma transition misc DNA methylation and SNP interaction misc Th2 pathway
topic_unstemmed	misc Asthma risk misc Asthma transition misc DNA methylation and SNP interaction misc Th2 pathway
topic_browse	misc Asthma risk misc Asthma transition misc DNA methylation and SNP interaction misc Th2 pathway
format_facet	Elektronische Aufsätze Aufsätze Elektronische Ressource
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title	The interplay of DNA methylation over time with Th2 pathway genetic variants on asthma risk and temporal asthma transition
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title_full	The interplay of DNA methylation over time with Th2 pathway genetic variants on asthma risk and temporal asthma transition
author_sort	Zhang, Hongmei
journal	Clinical epigenetics
journalStr	Clinical epigenetics
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author_browse	Zhang, Hongmei Tong, Xin Holloway, John W Rezwan, Faisal I Lockett, Gabrielle A Patil, Veeresh Ray, Meredith Everson, Todd M Soto-Ramírez, Nelís Arshad, S Hasan Ewart, Susan Karmaus, Wilfried
container_volume	6
format_se	Elektronische Aufsätze
author-letter	Zhang, Hongmei
doi_str_mv	10.1186/1868-7083-6-8
title_sort	interplay of dna methylation over time with th2 pathway genetic variants on asthma risk and temporal asthma transition
title_auth	The interplay of DNA methylation over time with Th2 pathway genetic variants on asthma risk and temporal asthma transition
abstract	Background Genetic effects on asthma of genes in the T-helper 2 (Th2) pathway may interact with epigenetic factors including DNA methylation. We hypothesized that interactions between genetic variants and methylation in genes in this pathway (IL4, IL4R, IL13, GATA3, and STAT6) influence asthma risk, that such influences are age-dependent, and that methylation of some CpG sites changes over time in accordance with asthma transition. We tested these hypotheses in subsamples of girls from a population-based birth cohort established on the Isle of Wight, UK, in 1989. Results Logistic regression models were applied to test the interaction effect of DNA methylation and SNP on asthma within each of the five genes. Bootstrapping was used to assess the models identified. From 1,361 models fitted at each age of 10 and 18 years, 8 models, including 4 CpGs and 8 SNPs, showed potential associations with asthma risk. Of the 4 CpGs, methylation of cg26937798 (IL4R) and cg23943829 (IL4) changes between ages 10 and 18 (both higher at 10; P = 9.14 × $ 10^{−6} $ and 1.07 × $ 10^{−5} $, respectively). At age 10, the odds of asthma tended to decrease as cg12405139 (GATA3) methylation increased (log-OR = −12.15; P = 0.049); this effect disappeared by age 18. At age 18, methylation of cg09791102 (IL4R) was associated with higher risk of asthma among subjects with genotype GG compared to AG (P = 0.003), increased cg26937798 methylation among subjects with rs3024685 (IL4R) genotype AA (P = 0.003) or rs8832 (IL4R) genotype GG (P = 0.01) was associated with a lower asthma risk; these CpGs had no effect at age 10. Increasing cg26937798 methylation over time possibly reduced the risk of positive asthma transition (asthma-free at age 10 → asthma at age 18; log-OR = −3.11; P = 0.069) and increased the likelihood of negative transition (asthma at age 10 → asthma-free at age 18; log-OR = 3.97; P = 0.074). Conclusions The interaction of DNA methylation and SNPs in Th2 pathway genes is likely to contribute to asthma risk. This effect may vary with age. Methylation of some CpGs changed over time, which may influence asthma transition. © Zhang et al.; licensee BioMed Central Ltd. 2014
abstractGer	Background Genetic effects on asthma of genes in the T-helper 2 (Th2) pathway may interact with epigenetic factors including DNA methylation. We hypothesized that interactions between genetic variants and methylation in genes in this pathway (IL4, IL4R, IL13, GATA3, and STAT6) influence asthma risk, that such influences are age-dependent, and that methylation of some CpG sites changes over time in accordance with asthma transition. We tested these hypotheses in subsamples of girls from a population-based birth cohort established on the Isle of Wight, UK, in 1989. Results Logistic regression models were applied to test the interaction effect of DNA methylation and SNP on asthma within each of the five genes. Bootstrapping was used to assess the models identified. From 1,361 models fitted at each age of 10 and 18 years, 8 models, including 4 CpGs and 8 SNPs, showed potential associations with asthma risk. Of the 4 CpGs, methylation of cg26937798 (IL4R) and cg23943829 (IL4) changes between ages 10 and 18 (both higher at 10; P = 9.14 × $ 10^{−6} $ and 1.07 × $ 10^{−5} $, respectively). At age 10, the odds of asthma tended to decrease as cg12405139 (GATA3) methylation increased (log-OR = −12.15; P = 0.049); this effect disappeared by age 18. At age 18, methylation of cg09791102 (IL4R) was associated with higher risk of asthma among subjects with genotype GG compared to AG (P = 0.003), increased cg26937798 methylation among subjects with rs3024685 (IL4R) genotype AA (P = 0.003) or rs8832 (IL4R) genotype GG (P = 0.01) was associated with a lower asthma risk; these CpGs had no effect at age 10. Increasing cg26937798 methylation over time possibly reduced the risk of positive asthma transition (asthma-free at age 10 → asthma at age 18; log-OR = −3.11; P = 0.069) and increased the likelihood of negative transition (asthma at age 10 → asthma-free at age 18; log-OR = 3.97; P = 0.074). Conclusions The interaction of DNA methylation and SNPs in Th2 pathway genes is likely to contribute to asthma risk. This effect may vary with age. Methylation of some CpGs changed over time, which may influence asthma transition. © Zhang et al.; licensee BioMed Central Ltd. 2014
abstract_unstemmed	Background Genetic effects on asthma of genes in the T-helper 2 (Th2) pathway may interact with epigenetic factors including DNA methylation. We hypothesized that interactions between genetic variants and methylation in genes in this pathway (IL4, IL4R, IL13, GATA3, and STAT6) influence asthma risk, that such influences are age-dependent, and that methylation of some CpG sites changes over time in accordance with asthma transition. We tested these hypotheses in subsamples of girls from a population-based birth cohort established on the Isle of Wight, UK, in 1989. Results Logistic regression models were applied to test the interaction effect of DNA methylation and SNP on asthma within each of the five genes. Bootstrapping was used to assess the models identified. From 1,361 models fitted at each age of 10 and 18 years, 8 models, including 4 CpGs and 8 SNPs, showed potential associations with asthma risk. Of the 4 CpGs, methylation of cg26937798 (IL4R) and cg23943829 (IL4) changes between ages 10 and 18 (both higher at 10; P = 9.14 × $ 10^{−6} $ and 1.07 × $ 10^{−5} $, respectively). At age 10, the odds of asthma tended to decrease as cg12405139 (GATA3) methylation increased (log-OR = −12.15; P = 0.049); this effect disappeared by age 18. At age 18, methylation of cg09791102 (IL4R) was associated with higher risk of asthma among subjects with genotype GG compared to AG (P = 0.003), increased cg26937798 methylation among subjects with rs3024685 (IL4R) genotype AA (P = 0.003) or rs8832 (IL4R) genotype GG (P = 0.01) was associated with a lower asthma risk; these CpGs had no effect at age 10. Increasing cg26937798 methylation over time possibly reduced the risk of positive asthma transition (asthma-free at age 10 → asthma at age 18; log-OR = −3.11; P = 0.069) and increased the likelihood of negative transition (asthma at age 10 → asthma-free at age 18; log-OR = 3.97; P = 0.074). Conclusions The interaction of DNA methylation and SNPs in Th2 pathway genes is likely to contribute to asthma risk. This effect may vary with age. Methylation of some CpGs changed over time, which may influence asthma transition. © Zhang et al.; licensee BioMed Central Ltd. 2014
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title_short	The interplay of DNA methylation over time with Th2 pathway genetic variants on asthma risk and temporal asthma transition
url	https://dx.doi.org/10.1186/1868-7083-6-8
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author2	Tong, Xin Holloway, John W Rezwan, Faisal I Lockett, Gabrielle A Patil, Veeresh Ray, Meredith Everson, Todd M Soto-Ramírez, Nelís Arshad, S Hasan Ewart, Susan Karmaus, Wilfried
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The interplay of DNA methylation over time with Th2 pathway genetic variants on asthma risk and temporal asthma transition

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