Dataset Information

Association between AXL promoter methylation and lung function growth during adolescence.

ABSTRACT: AXL is one of the TAM (TYRO3, AXL and MERTK) receptor tyrosine kinases and may be involved in airway inflammation. Little is known about how epigenetic changes in AXL may affect lung development during adolescence. We investigated the association between AXL DNA methylation at birth and lung function growth from 10 to 18 years of age in 923 subjects from the Children's Health Study (CHS). DNA methylation from newborn bloodspots was measured at multiple CpG loci across the regulatory regions of AXL using Pyrosequencing. Linear spline mixed-effects models were fitted to assess the association between DNA methylation and 8-year lung function growth. Findings were evaluated for replication in a separate population of 237 CHS subjects using methylation data from the Illumina HumanMethylation450 (HM450) array when possible. A 5% higher average methylation level of the AXL promoter region at birth was associated with a 48.4 ml decrease in mean FEV₁ growth from 10 to 18 years of age in the primary study population (95% CI: -100.2, 3.4), and a 53.9 ml decrease in mean FEV₁ growth from 11 to 15 years of age in the replication population (95% CI: -104.3, -3.5). One CpG locus in the promoter region, cg10564498, was significantly associated with decreased growth in FEV₁, FVC and MMEF from 10 to 18 years of age and the negative associations were observed in a similar age range in the replication population. These findings suggest a potential association between AXL promoter methylation at birth and lower lung function growth during adolescence.

SUBMITTER: Gao L

PROVIDER: S-EPMC6342069 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Association between AXL promoter methylation and lung function growth during adolescence.

Gao Lu L Urman Robert R Millstein Joshua J Siegmund Kimberly D KD Dubeau Louis L Breton Carrie V CV

Epigenetics 20181019 10-11

AXL is one of the TAM (TYRO3, AXL and MERTK) receptor tyrosine kinases and may be involved in airway inflammation. Little is known about how epigenetic changes in AXL may affect lung development during adolescence. We investigated the association between AXL DNA methylation at birth and lung function growth from 10 to 18 years of age in 923 subjects from the Children's Health Study (CHS). DNA methylation from newborn bloodspots was measured at multiple CpG loci ...[more]

PMID: 30277126

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Project description:BackgroundAdolescence is a significant period for the gender-dependent development of lung function. Prior studies have shown that DNA methylation (DNA-M) is associated with lung function and DNA-M at some cytosine-phosphate-guanine dinucleotide sites (CpGs) changes over time. This study examined whether changes of DNA-M at lung-function-related CpGs are associated with changes in lung function during adolescence for each gender, and if so, the biological significance of the detected CpGs.MethodsGenome-scale DNA-M was measured in peripheral blood samples at ages 10 (n = 330) and 18 years (n = 476) from the Isle of Wight (IOW) birth cohort in United Kingdom, using Illumina Infinium arrays (450 K and EPIC). Spirometry was conducted at both ages. A training and testing method was used to screen 402,714 CpGs for their potential associations with lung function. Linear regressions were applied to assess the association of changes in lung function with changes of DNA-M at those CpGs potentially related to lung function. Adolescence-related and personal and family-related confounders were included in the model. The analyses were stratified by gender. Multiple testing was adjusted by controlling false discovery rate of 0.05. Findings were further examined in two independent birth cohorts, the Avon Longitudinal Study of Children and Parents (ALSPAC) and the Children, Allergy, Milieu, Stockholm, Epidemiology (BAMSE) cohort. Pathway analyses were performed on genes to which the identified CpGs were mapped.ResultsFor females, 42 CpGs showed statistically significant associations with change in FEV1/FVC, but none for change in FEV1 or FVC. No CpGs were identified for males. In replication analyses, 16 and 21 of the 42 CpGs showed the same direction of associations among the females in the ALSPAC and BAMSE cohorts, respectively, with 11 CpGs overlapping across all the three cohorts. Through pathway analyses, significant biological processes were identified that have previously been related to lung function development.ConclusionsThe detected 11 CpGs in all three cohorts have the potential to serve as the candidate epigenetic markers for changes in lung function during adolescence in females.

Project description:BackgroundThe pattern of lung function development from pre-adolescence to adulthood plays a significant role in the pathogenesis of respiratory diseases. Inconsistent findings in genetic studies on lung function trajectories, the importance of DNA methylation (DNA-M), and the critical role of adolescence in lung function development motivated the present study of pre-adolescent DNA-M with lung function trajectories. This study investigated epigenome-wide associations of DNA-M at cytosine-phosphate-guanine dinucleotide sites (CpGs) at childhood with lung function trajectories from childhood to young adulthood.MethodsDNA-M was measured in peripheral blood at age 10 years in the Isle of Wight (IOW) birth cohort. Spirometry was conducted at ages 10, 18, and 26 years. A training/testing-based method was used to screen CpGs. Multivariable logistic regressions were applied to assess the association of DNA-M with lung function trajectories from pre-adolescence to adulthood. To detect differentially methylated regions (DMRs) among CpGs, DMR enrichment analysis was conducted. Findings were further tested in the Avon Longitudinal Study of Parents and Children (ALSPAC) cohort. Pathway analyses were performed on the mapped genes of the identified CpGs and DMRs. Biological relevance of the identified CpGs was assessed with gene expression. All analyses were stratified by sex.ResultsHigh and low trajectories of FVC, FEV1, and FEV1/FVC in each sex were identified. At PBonferroni < 0.05, DNA-M at 96 distinct CpGs (41 in males) showed associations with FVC, FEV1, and FEV1/FVC trajectories in IOW cohort. These 95 CpGs (cg24000797 was disqualified) were further tested in ALSPAC; 44 CpGs (19 in males) of these 95 showed the same directions of association as in the IOW cohort; and three CpGs (two in males) were replicated. DNA-M at two and four CpGs showed significant associations with the corresponding gene expression in males and females, respectively. At PFDR < 0.05, 23 and 10 DMRs were identified in males and females, respectively. Pathways were identified; some of those were linked to lung function and chronic obstructive lung diseases.ConclusionThe identified CpGs at pre-adolescence have the potential to serve as candidate markers for lung function trajectory prediction and chronic lung diseases.

Project description:ObjectivesSchool racial/ethnic segregation in U.S. schoolsDifferences in school racial/ethnic composition may increase health disparities by concentrating educational opportunities that confer long-term health benefits in schools serving predominantly wwhite students. For racial minority students, high concentrations of white students may increase exposure to racismis also associated with psychologicstress, which may ultimately reduceing the long-term health benefits from educational opportunities. Meanwhile associations of racial/ethnic academic tacking within schools and health have been mixed. We sought to test whether: 1) differences in racial/ethnic composition between schools and, 2) racial/ethnic distribution of students in academic tracks within schools are associated with long-term health benefits or risks for white, Black and Latinx students.MethodsWe analyzed the National Longitudinal Study of Adolescent to Adult Health (12,438 participants, collected 1994-2008), to test whether the school-level segregation (percent of non-Latinx white students at participants' school during adolescence) was associated with adult health outcomes at ages 18-26 & 24-32, controlling for contextual factorscomparing Black, Latinx, and white students, and controlling for contextualf factors. A secondary analysis explored whether racial/ethnic cohorting across levels of English courses was associated with each health outcome.ResultsAttending a school with a higher percent of white students was associated with higher adult depression scores, substance abuse, and worse self-rated health for black Black students; lower depression scores, better self-rated health, and alcohol abuse for white students; and no health differences for Latinx students. Greater within school racial/ethnic cohorting across English courses was associated with increased odds of alcohol abuse for white students; decreased odds of alcohol abuse for Black and Latinx students; and decreased odds of drug abuse for Black students.ConclusionAmong Bblack youth, attending a school with a higher percentage of white students is associated with worse behavioral health in adulthood. Understanding the potential impacts of school racial/ethnic composition on health is critical to designing policies that maximize access to opportunity and health.Education policies should comprehensively address school quality and racism to maximize adult health.

Dataset Information

Association between AXL promoter methylation and lung function growth during adolescence.

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Association between <i>AXL</i> promoter methylation and lung function growth during adolescence.

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