British Genomics Study Looks at Hereditary Thyroid Hormone Variations

Data accumulated during the intense study of two population groups in the United Kingdom has been mined for information related to the hereditary basis of thyroid hormone variations.

Normal thyroid function is essential for health, but its genetic architecture remains poorly understood. To increase understanding of this factor for the heritable thyroid hormones thyrotropin (TSH) and free thyroxine (FT4), investigators linked to the Wellcome Trust Sanger Institute's (Hinxton, United Kingdom) UK10K project analyzed whole-genome sequence data from two well-studied population groups.


The Avon Longitudinal Study of Parents and Children (ALSPAC) includes more than 14,000 mothers enrolled during pregnancy in 1991 and 1992, and the health and development of their children has been followed in great detail ever since. The ALSPAC families have provided a vast amount of genetic and environmental information over the years. The TwinsUK Adult Twin Registry is cited as being the most detailed clinical adult register in the world. It comprises 11,000 identical and non-identical twins between the ages of 16 and 85 years who have generated a database used to study the genetic and environmental etiology of age-related complex traits and diseases.

Meta-analysis results for common variants associated with TSH and FT4 led to the identification of a novel variant in the SYN2 (synapsin II) gene linked to TSH, as well as a new independent variant in the PDE8B (phosphodiesterase 8B) gene. For FT4, the investigators identified a low-frequency variant near B4GALT6 (B-N-acetylglucosaminyl-glycopeptide b-1,4-galactosyltransferase)/SLC25A52 (solute carrier family 25, member 52) and a rare TTR (transthyretin, a serum and cerebrospinal fluid carrier of the thyroid hormone thyroxine) variant. All common variants explained about 20% of the variance in TSH and FT4.

Contributing author Dr. Nicholas Timpson, reader in genetic epidemiology at the University of Bristol (United Kingdom) and co-chair of the UK10K whole genome sequencing initiative, said, “This work is another example of how extending gene studies to include whole genome sequencing can identify new clinically informative variants and enhance our understanding of key biological processes. The UK10K project has been essential to this endeavor and we are now beginning to realize its potential."

Related Links:
Wellcome Trust Sanger Institute
University of Bristol