Research Research awards BTF Research Award 2011 Thyroid Function and Body Composition in Children: cause or effect? A study using Mendelian Randomization Dr Peter Taylor, Centre for Endocrine and Diabetes and Sciences, University Hospital Wales Final report We were very grateful to receive the £10,000 research award from the British Thyroid Research Foundation in November 2011. This enabled us to perform 1,200 thyroid function tests in children in the Avon Longitudinal Study of Parents and Children (ALSPAC) from stored samples taken at ages 7 and 15. ALSPAC is regarded as Europe's premier observational study in children, and to our knowledge, it is the only cohort in the world, which has stored blood samples from early childhood and serial detailed measurements of body composition such as height and fat mass as well as key measurements of bone development throughout childhood. ALSPAC also has detailed information regarding the children's genetic make-up and their environment (e.g. social class). Overall this project provided us with the unique opportunity to study the relationships between thyroid hormone levels, body composition and bone development at different stages of childhood development. A greater understanding of the impact of thyroid horomone on both body composition and bone architecture is essential in understanding future causes of adult ill health such as obesity, development of the metabolic syndrome and osteoporosis. Our results showed that there were key changes in one of the thyroid hormones, free tri-iodothyronine (FT3) over childhood, which varied considerably over time in the same individual, unlike free thyroxine (FT4) and thyroid stimulating hormone (TSH) which were more stable. Younger children also appear to have substantially higher levels of FT3 than adults, which merits further study. Only FT3 was substantially associated with body composition and bone development in childhood. Surprisingly FT3 was positively associated with fat mass, i.e. children with higher levels of fat mass had higher levels of FT3; which is perhaps counter intuitive given that higher levels of thyroid hormones are usually associated with weight loss. Statistical and simple genetic analyses raised the possibility that fat mass was involved in the conversion of thyroid hormone; further genetic analyses and laboratory studies are required to clarify this. This relationship between fat mass and FT3 is integral to the relationship between FT3 and bone as the association between FT3 and bone was lost after accounting for an individual's fat mass. Furthermore we also found preliminary evidence that the genes which influence thyroid function are different between children and adults. This has two fold relevance i) Genetic association studies of thyroid function are becoming increasingly common and children and adults should potentially be analysed separately. ii) It also has important implications for our understanding of the role of thyroid hormone in childhood development, as thyroid hormone may influence developmental processes differently over childhood. Overall, by following the same children from age 7 to age 15 through the stored blood samples from the ALSPAC cohort, we have shown that FT3 levels are higher in pre-pubertal children and fall as the children approach adulthood. The higher FT3 levels were surprisingly associated with greater fat mass and appeared to be controlled by different genes from those that play a role in older children. Taken together, this is the first large prospective cohort study to indicate that FT3 may play a different role in children and may be linked to changes in body composition that are relevant later on in life.