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,...
Ausführliche Beschreibung
Autor*in: |
Zhang, Hongmei [verfasserIn] |
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E-Artikel |
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Englisch |
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2014 |
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Anmerkung: |
© Zhang et al.; licensee BioMed Central Ltd. 2014 |
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Übergeordnetes Werk: |
Enthalten in: Clinical epigenetics - [S.l.] : BioMed Central, 2010, 6(2014), 1 vom: 15. Apr. |
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Übergeordnetes Werk: |
volume:6 ; year:2014 ; number:1 ; day:15 ; month:04 |
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DOI / URN: |
10.1186/1868-7083-6-8 |
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Katalog-ID: |
SPR030671140 |
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245 | 1 | 4 | |a The interplay of DNA methylation over time with Th2 pathway genetic variants on asthma risk and temporal asthma transition |
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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. | ||
650 | 4 | |a Asthma risk |7 (dpeaa)DE-He213 | |
650 | 4 | |a Asthma transition |7 (dpeaa)DE-He213 | |
650 | 4 | |a DNA methylation and SNP interaction |7 (dpeaa)DE-He213 | |
650 | 4 | |a Th2 pathway |7 (dpeaa)DE-He213 | |
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700 | 1 | |a Holloway, John W |4 aut | |
700 | 1 | |a Rezwan, Faisal I |4 aut | |
700 | 1 | |a Lockett, Gabrielle A |4 aut | |
700 | 1 | |a Patil, Veeresh |4 aut | |
700 | 1 | |a Ray, Meredith |4 aut | |
700 | 1 | |a Everson, Todd M |4 aut | |
700 | 1 | |a Soto-Ramírez, Nelís |4 aut | |
700 | 1 | |a Arshad, S Hasan |4 aut | |
700 | 1 | |a Ewart, Susan |4 aut | |
700 | 1 | |a Karmaus, Wilfried |4 aut | |
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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 |
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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 |
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interplay of dna methylation over time with th2 pathway genetic variants on asthma risk and temporal asthma transition |
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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 |
collection_details |
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container_issue |
1 |
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 |
author2Str |
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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up_date |
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