Browsing by Author "Karmaus, Wilfried"

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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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    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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    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.