First whole genome sequencing study to explore the genetic make-up of thyroid function discovers new gene association

The results of the study 'Whole genome sequence based analysis of thyroid function' were published in the leading international scientific journal Nature Communications in March 2015.

Dr Peter Taylor, winner of the BTF Research Award 2014 was joint author of the study. He comments: 'Thyroid hormone levels are very important for childhood development and adult health. It is now becoming increasingly recognised that even modest variations in thyroid hormone levels have a substantial impact on health. Interestingly twin studies have already indicated that in healthy individuals' thyroid hormones are largely genetically determined, but the genetic make-up of thyroid function remains largely unknown.

To date only common genetic variants have been studied in detail in large populations. However this has only explained a fraction of the genetic variation in thyroid function. The UK10K project ( was set up using enhanced gene sequencing to enable researchers to understand the link between low-frequency and rare genetic changes, which can result in key changes to the proteins that control cell processes. Data were collected from 4000 people in the UK and leading epidemiological cohorts in Europe and Australia

As well as identifying two new common variants in two genes associated with thyroid function, we identified an uncommon variant, which actually was near a known rare variant associated with familial dysalbuminemic hyperthyroxinemia (a rare condition which amongst other metabolic abnormalities leads to higher thyroid hormone levels). We also discovered rare variants associated with thyroid function in the region of the genome in NRG1 whose protein is essential for the development of the brain and the heart.

Further analysis identified that common genetic variants only explain about 20% of the total variation in thyroid function. Therefore further studies of rarer variants will yield new insights into thyroid physiology. Given the relatively large impact of the rarer variants we identified it is possible that in some individuals with borderline thyroid hormone levels this is due to a handful of rarer variants rather than overt auto-immune disease, this may have implications for their treatment.'

The paper is freely available on the Nature website.

Dr Taylor added: 'I would like to thank the BTF for their continued support, as BTF funds enabled the measurement of some of the thyroid hormone levels in one of the key study groups'.