B4639 - Understanding the role of epigenetic regulation of thyroid function using data from TWINS UK and ALSPAC cohorts - 11/06/2024

B number: 
Principal applicant name: 
Hannah Hickingbotham | Bristol Royal Hospital for Children University Hospitals Bristol & Weston Foundation Trust
Dr Toby Candler, Dr Matt Silver
Title of project: 
Understanding the role of epigenetic regulation of thyroid function using data from TWINS UK and ALSPAC cohorts
Proposal summary: 

DNA methylation (chemical marks on the DNA code) can change the activity of genes and how our cells function. There is evidence that mother’s environment can influence her baby’s DNA methylation and have lasting health consequences.

Little is known about how DNA methylation affects the genes related to the thyroid gland but it could be an important factor in thyroid disease and health.

Using large established datasets (TWINS-UK, ALSPAC), we will explore how DNA methylation at important areas of the genetic code influences thyroid hormone production in children and how the mother’s environment may contribute to these DNA methylation changes.

Impact of research: 
The effect of epigenetic variation on thyroid development and function is an area with limited studies. Initial studies point to an environmental link between PAX8 methylation and thyroid phenotype. Studies have described seasonal variation in the incidence of congenital hypothyroidism and thus it is important to explore epigenetic causes and environmental influence. This study would provide insights into the relationship between PAX8 methylation and thyroid function across a large cohort and specifically in twins. It also provides the opportunity to explore periconceptual environmental factors. By understanding more about the impact of the periconceptual environment and the role of epigenetics in regulating thyroid function we can plan further studies to explore periconceptional interventions (e.g. nutritional) that may limit congenital hypothyroidism, which is especially important for those countries without screening. Understanding more about the epigenetic role in thyroid function would also support further work into the fundamental biology of thyroid regulation. We are liasing with the Costagliola lab in Brussels and the Pediatric Endocrinology Department at Universitatsmedizin, Berlin exploring future research opportunities using stem cells to investigate PAX8 methylation and thyroid function and hope that this research would support these collaborations. Establishing the link between maternal environment, DNA methylation and the impact on the thyroid through this research will provide the basis for a larger grant application for research at both a cellular level and across other datasets. We plan to disseminate our research through publications and conference presentations.
Date proposal received: 
Monday, 10 June, 2024
Date proposal approved: 
Tuesday, 11 June, 2024
Epigenetic epidemiology , Thyroid disease Congenital hypothyroidism, Epigenome-wide association study Statistical methods, Epigenome-wide association Periconceptional and gestational factors Hormones - thyroid Statistical methods