Browsing by Author "Zhang, Hongmei"

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    Changes in DNA methylation from pre- to post-adolescence are associated with pubertal exposures
    (BMC (part of Springer Nature), 2019-12-02) Han, Luhang; Zhang, Hongmei; Kaushal, Akhilesh; Rezwan, Faisal I.; Kadalayil, Latha; Karmaus, Wilfried; Henderson, A. John; Relton, Caroline L.; Ring, Susan; Arshad, Syed Hasan; Holloway, John W.
    Background Adolescence is a period characterized by major biological development, which may be associated with changes in DNA methylation (DNA-M). However, it is unknown to what extent DNA-M varies from pre- to post-adolescence, whether the pattern of changes is different between females and males, and how adolescence-related factors are associated with changes in DNA-M. Methods Genome-scale DNA-M at ages 10 and 18 years in whole blood of 325 subjects (n = 140 females) in the Isle of Wight (IOW) birth cohort was analyzed using Illumina Infinium arrays (450K and EPIC). Linear mixed models were used to examine DNA-M changes between pre- and post-adolescence and whether the changes were gender-specific. Adolescence-related factors and environmental exposure factors were assessed on their association with DNA-M changes. Replication of findings was attempted in the comparable Avon Longitudinal Study of Parents and Children (ALSPAC) cohort. Results In the IOW cohort, after controlling for technical variation and cell compositions at both pre- and post-adolescence, 15,532 cytosine–phosphate–guanine (CpG) sites (of 400,825 CpGs, 3.88%) showed statistically significant DNA-M changes from pre-adolescence to post-adolescence invariant to gender (false discovery rate (FDR) = 0.05). Of these 15,532 CpGs, 10,212 CpGs (66%) were replicated in the ALSPAC cohort. Pathway analysis using Ingenuity Pathway Analysis (IPA) identified significant biological pathways related to growth and development of the reproductive system, emphasizing the importance of this period of transition on epigenetic state of genes. In addition, in IOW, we identified 1179 CpGs with gender-specific DNA-M changes. In the IOW cohort, body mass index (BMI) at age 10 years, age of growth spurt, nonsteroidal drugs use, and current smoking status showed statistically significant associations with DNA-M changes at 15 CpGs on 14 genes such as the AHRR gene. For BMI at age 10 years, the association was gender-specific. Findings on current smoking status were replicated in the ALSPAC cohort. Conclusion Adolescent transition is associated with changes in DNA-M at more than 15K CpGs. Identified pathways emphasize the importance of this period of transition on epigenetic state of genes relevant to cell growth and immune system development.
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    Changes of DNA methylation are associated with changes in lung function during adolescence
    (BioMed Central, 2020-04-07) Sunny, Shadia Khan; Zhang, Hongmei; Rezwan, Faisal I.; Relton, Caroline L.; Henderson, A. John; Merid, Simon Kebede; Melén, Erik; Hallberg, Jenny; Arshad, Syed Hasan; Ewart, Susan; Holloway, John W.
    Background Adolescence 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. Methods Genome-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. Results For 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. Conclusions The 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
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    Epigenome-wide association study reveals duration of breastfeeding is associated with epigenetic differences in children
    (MDPI, 2020-05-20) Sherwood, William B.; Kothalawala, Dilini M.; Kadalayil, Latha; Ewart, Susan; Zhang, Hongmei; Karmaus, Wilfried; Arshad, Syed Hasan; Holloway, John W.; Rezwan, Faisal I.
    Several small studies have shown associations between breastfeeding and genome-wide DNA methylation (DNAm). We performed a comprehensive Epigenome-Wide Association Study (EWAS) to identify associations between breastfeeding and DNAm patterns in childhood. We analysed DNAm data from the Isle of Wight Birth Cohort at birth, 10, 18 and 26 years. The feeding method was categorized as breastfeeding duration >3 months and >6 months, and exclusive breastfeeding duration >3 months. EWASs using robust linear regression were performed to identify differentially methylated positions (DMPs) in breastfed and non-breastfed children at age 10 (false discovery rate of 5%). Differentially methylated regions (DMRs) were identified using comb-p. The persistence of significant associations was evaluated in neonates and individuals at 18 and 26 years. Two DMPs, in genes SNX25 and LINC00840, were significantly associated with breastfeeding duration >6 months at 10 years and was replicated for >3 months of exclusive breastfeeding. Additionally, a significant DMR spanning the gene FDFT1 was identified in 10-year-old children who were exposed to a breastfeeding duration >3 months. None of these signals persisted to 18 or 26 years. This study lends further support for a suggestive role of DNAm in the known benefits of breastfeeding on a child’s future health
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    Epigenome-wide meta-analysis of blood DNA methylation in newborns and children identifies numerous loci related to gestational age
    (BioMed Central, 2020-03-02) Merid, Simon Kebede; Novoloaca, Alexei; Sharp, Gemma C.; Küpers, Leanne K.; Kho, Alvin T.; Roy, Ritu; Gao, Lu; Annesi-Maesano, Isabella; Jain, Pooja; Plusquin, Michelle; Kogevinas, Manolis; Allard, Catherine; Vehmeijer, Florianne O. L.; Kazmi, Nabila; Salas, Lucas A.; Rezwan, Faisal I.; Zhang, Hongmei; Sebert, Sylvain; Czamara, Darina; Rifas-Shiman, Sheryl L.; Melton, Phillip E.; Lawlor, Debbie A.; Pershagen, Göran; Breton, Carrie V.; Huen, Karen
    Background Preterm birth and shorter duration of pregnancy are associated with increased morbidity in neonatal and later life. As the epigenome is known to have an important role during fetal development, we investigated associations between gestational age and blood DNA methylation in children. Methods We performed meta-analysis of Illumina’s HumanMethylation450-array associations between gestational age and cord blood DNA methylation in 3648 newborns from 17 cohorts without common pregnancy complications, induced delivery or caesarean section. We also explored associations of gestational age with DNA methylation measured at 4–18 years in additional pediatric cohorts. Follow-up analyses of DNA methylation and gene expression correlations were performed in cord blood. DNA methylation profiles were also explored in tissues relevant for gestational age health effects: fetal brain and lung. Results We identified 8899 CpGs in cord blood that were associated with gestational age (range 27–42 weeks), at Bonferroni significance, P < 1.06 × 10− 7, of which 3343 were novel. These were annotated to 4966 genes. After restricting findings to at least three significant adjacent CpGs, we identified 1276 CpGs annotated to 325 genes. Results were generally consistent when analyses were restricted to term births. Cord blood findings tended not to persist into childhood and adolescence. Pathway analyses identified enrichment for biological processes critical to embryonic development. Follow-up of identified genes showed correlations between gestational age and DNA methylation levels in fetal brain and lung tissue, as well as correlation with expression levels. Conclusions We identified numerous CpGs differentially methylated in relation to gestational age at birth that appear to reflect fetal developmental processes across tissues. These findings may contribute to understanding mechanisms linking gestational age to health effects.
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    Gaussian Bayesian network comparisons with graph ordering unknown
    (Elsevier, 2020-12-26) Zhang, Hongmei; Huang, Xianzheng; Han, Shengtong; Rezwan, Faisal I.; Karmaus, Wilfried; Arshad, Syed Hasan; Holloway, John W.
    A Bayesian approach is proposed that unifies Gaussian Bayesian network constructions and comparisons between two networks (identical or differential) for data with graph ordering unknown. When sampling graph ordering, to escape from local maximums, an adjusted single queue equi-energy algorithm is applied. The conditional posterior probability mass function for network differentiation is derived and its asymptotic proposition is theoretically assessed. Simulations are used to demonstrate the approach and compare with existing methods. Based on epigenetic data at a set of DNA methylation sites (CpG sites), the proposed approach is further examined on its ability to detect network differentiations. Findings from theoretical assessment, simulations, and real data applications support the efficacy and efficiency of the proposed method for network comparisons.
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    Pre-adolescence DNA methylation is associated with BMI status change from pre-to post-adolescence
    (BMC (part of Springer Nature), 2021-03-25) Wang, Jiajing; Zhang, Hongmei; Rezwan, Faisal I.; Relton, Caroline L.; Hasan Arshad, S.; Holloway, John W.
    Background: Previous studies have shown that DNA methylation (DNAm) is associated with body mass index (BMI). However, it is unknown whether DNAm at pre-adolescence is associated with BMI status transition from pre- to postadolescence. In the Isle of Wight (IoW) birth cohort, genome-wide DNA methylation in whole blood was measured using Illumina Infnium Human450 and EPIC BeadChip arrays in n=325 subjects, and pre- to post-adolescence BMI transition was classifed into four groups: (1) normal to normal, (2) normal to overweight or obese, (3) overweight or obese to normal, and (4) persistent overweight or obese. We used recursive random forest to screen genome-wide Cytosine-phosphate-Guanine (CpG) sites with DNAm potentially associated with BMI transition for each gender, and the association of BMI status transition with DNAm at an earlier age was assessed via logistic regressions. To evaluate gender specifcity, interactions between DNAm and gender were included in the model. Findings in the IoW cohort were further tested in an independent cohort, the Avon Longitudinal Study of Parents and Children (ALSPAC). Results: In total, 174 candidate CpGs were selected including CpGs from screening and CpGs previously associated correctionally with BMI in children and adults. Of these 174 CpGs, pre-adolescent DNAm of 38 CpGs in the IoW cohort was associated with BMI status transition, including 30 CpGs showing gender-specifc associations. Thirteen CpGs showed consistent associations between the IoW cohort and the ALSPAC cohort (11 of which were gender-specifc). Conclusion: Pre-adolescence DNAm is associated with the change in BMI status from pre- to post-adolescence and such associations are likely to be gender-specifc