Publications by authors named "Clarke-Harris R"

Epigenetics links perinatal influences with later obesity. We identifed differentially methylated CpG (dmCpG) loci measured at 17 years associated with concurrent adiposity measures and examined whether these were associated with hsCRP, adipokines, and early life environmental factors. Genome-wide DNA methylation from 1192 Raine Study participants at 17 years, identified 29 dmCpGs (Bonferroni corrected p < 1.

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  • The study investigates how early life DNA methylation of the SLC6A4 gene could predict later obesity and metabolic issues, linking it to serotonin levels and energy regulation.
  • Researchers measured DNA methylation in different populations: children, adolescents, and adults using various methods, including pyrosequencing.
  • Results showed that lower methylation of a specific site (CpG5) on the SLC6A4 gene was associated with higher fat mass and skinfold thickness in children and adolescents, indicating that maternal factors also play a role.
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Background: There is now increasing evidence that asthma and atopy originate in part in utero, with disease risk being associated with the altered epigenetic regulation of genes.

Objective And Methods: To determine the relationship between variations in DNA methylation at birth and the development of allergic disease, we examined the methylation status of CpG loci within the promoter regions of Th1/2 lineage commitment genes (GATA3, IL-4, IL-4R, STAT4 and TBET) in umbilical cord DNA at birth in a cohort of infants from the Southampton Women's Survey (n = 696) who were later assessed for asthma, atopic eczema and atopy.

Results: We found that higher methylation of GATA3 CpGs -2211/-2209 at birth was associated with a reduced risk of asthma at ages 3 (median ratio [median methylation in asthma group/median methylation in non-asthma group] = 0.

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  • Early life environment significantly influences obesity risk through epigenetic changes, specifically DNA methylation.
  • A novel link was found between methylation levels of the ANRIL gene at birth and increased childhood adiposity by age six, supported by findings in diverse populations.
  • This study suggests that methylation patterns are meaningful indicators of future weight gain and highlight the importance of early environmental factors on long-term health outcomes.
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  • * Researchers studied how DNA methylation at a specific region of the CDKN2A gene (related to fat and bone cells) at birth affects bone mass in children at ages 4 and 6.
  • * Higher levels of DNA methylation were linked to lower bone mass and density, indicating that early genetic regulation could impact bone health in childhood.
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  • Early life environments play a crucial role in shaping long-term neurocognitive development through epigenetic changes, yet the evidence in humans was previously limited.
  • The study analyzed DNA methylation at birth and its link to children's neuropsychological outcomes in two diverse populations, finding specific methylation patterns related to cognitive function.
  • Results highlighted that higher methylation of the HES1 gene at birth was associated with better cognitive abilities later on, reinforcing the idea that early environmental factors can lead to lasting changes in brain development and behavior through epigenetic mechanisms.
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Background: Studies in animal models and in cultured cells have shown that fatty acids can induce alterations in the DNA methylation of specific genes. There have been no studies of the effects of fatty acid supplementation on the epigenetic regulation of genes in adult humans.

Methods And Results: We investigated the effect of supplementing renal patients with 4 g daily of either n-3 long-chain polyunsaturated fatty acids (n-3 LCPUFA) or olive oil (OO) for 8 weeks on the methylation status of individual CpG loci in the 5' regulatory region of genes involved in PUFA biosynthesis in peripheral blood mononuclear cells from men and women (aged 53 to 63 years).

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The early environment, acting via epigenetic processes, is associated with differential risk of cardiometabolic disease (CMD), which can be predicted by epigenetic marks in proxy tissues. However, such measurements at time points disparate from the health outcome or the environmental exposure may be confounded by intervening stochastic and environmental variation. To address this, we analyzed DNA methylation in the peroxisome proliferator-activated receptor γ coactivator 1α promoter in blood from 40 children (20 boys) collected annually between 5 and 14 years of age by pyrosequencing.

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Female humans and rodents have been shown to have higher 22:6n-3 status and synthesis than males. It is unclear which sex hormone is involved. We investigated the specificity of the effects of physiological concentrations of sex hormones in vitro on the mRNA expression of genes involved in polyunsaturated fatty acid (PUFA) biosynthesis and on the conversion of [d5]-18:3n-3 to longer chain fatty acids.

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