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Sex-specific epigenetic mediators between early life social disadvantage and adulthood BMI.

ABSTRACT: AIM:The objective of this study was to identify potential epigenetic mediating pathways linking early life social disadvantage (ELSD) to adulthood BMI. METHODS:Sex-specific epigenome-wide two-stage mediation analyses were conducted in blood and adipose tissue, and mediation estimates were obtained using cross-product mediation analysis. Pathway analyses were conducted using GREAT software (Bejerano Lab, CA, USA). RESULTS:Candidate mediation CpG sites were identified in adipose tissue, but not blood, and were sex-specific. Significant mediation sites in females included CpG loci in genes: PKHG1, BCAR3, ADAM5P, PIEZO1, FGFRL1, FASN and DPP9, among others. Pathway analyses revealed evidence of enrichment for processes associated with TFG-? signaling and immunologic signatures. In males, significant mediation loci included sites in MAP3K5 and RPTOR, which have previously been associated with adipogenesis, inflammation and insulin resistance. CONCLUSION:Our findings provide supportive evidence for the mediating role of epigenetic mechanisms in the effect of early life social disadvantage on adulthood BMI.

SUBMITTER: Chu SH

PROVIDER: S-EPMC6367732 | biostudies-literature | 2018 Jun

REPOSITORIES: biostudies-literature

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Sex-specific epigenetic mediators between early life social disadvantage and adulthood BMI.

Chu Su H SH Loucks Eric B EB Kelsey Karl T KT Gilman Stephen E SE Agha Golareh G Eaton Charles B CB Buka Stephen L SL Huang Yen-Tsung YT

Epigenomics 20180611 6

<h4>Aim</h4>The objective of this study was to identify potential epigenetic mediating pathways linking early life social disadvantage (ELSD) to adulthood BMI.<h4>Methods</h4>Sex-specific epigenome-wide two-stage mediation analyses were conducted in blood and adipose tissue, and mediation estimates were obtained using cross-product mediation analysis. Pathway analyses were conducted using GREAT software (Bejerano Lab, CA, USA).<h4>Results</h4>Candidate mediation CpG sites were identified in adip ...[more]

PMID: 29888956

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Project description:ObjectivesEarly-life adversities (ELAs) such as child maltreatment (neglect and abuse) and socioeconomic disadvantage have been associated with adult mortality. However, evidence is sparse for specific types of ELA. We aimed to establish whether specific ELAs (ie, different types of child maltreatment and socioeconomic disadvantage) were associated independently with all-cause mortality in mid-adulthood and to examine potential intermediary pathways.DesignProspective cohort study.Setting1958 British birth cohort: a longitudinal, population-based sample of individuals born in Great Britain during a single week in March 1958.Participants9310 males and females with data on child maltreatment and mortality (44/45-58 years).Outcome measuresMortality follow-up from 2002/2003 to 2016 when participants were aged 44/45-58 years. Death was ascertained via the NHS Central Register (N=296) or cohort maintenance activities (N=16).ResultsPrevalence of ELAs ranged from 1.6% (sexual abuse) to 11% (psychological abuse). Several, but not all, ELAs were associated with increased risk of premature death, independent of covariates and other adversities; adjusted HRs were 2.64 (95% CI 1.52 to 4.59) for sexual abuse, 1.93 (95% CI 1.45 to 2.58) for socioeconomic disadvantage, 1.73 (95% CI 1.11 to 2.71) for physical abuse and 1.43 (95% CI 1.03 to 1.98) for neglect. After adjustment for covariates and other adversities, no associations with mortality were observed for psychological and witnessing abuse. Regarding potential intermediaries (including adult socioeconomic factors, behaviours, adiposity, mental health and cardiometabolic markers), most associations attenuated after accounting for adult health behaviours (particularly smoking). In addition, early-life socioeconomic disadvantage and neglect associations attenuated after accounting for adult socioeconomic factors. The association for sexual abuse and premature mortality was largely unaffected by potential intermediaries.ConclusionsAssociations with premature mortality varied by type of ELA: associations for sexual and physical abuse, neglect and socioeconomic disadvantage were independent of each other. Different types of ELAs could influence premature mortality via different pathways; this requires further research.

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Sex-specific epigenetic mediators between early life social disadvantage and adulthood BMI.

Publications

Sex-specific epigenetic mediators between early life social disadvantage and adulthood BMI.

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