Researchers report new gene associated with thyroid levels

So another reason that TSH does not always and simply reflect thyroid hormone levels in the simplistic way we are often told it does. This time it is a gene - SYN2 (also NRG1 and ​CAPZB).

Researchers report new gene associated with thyroid levels

Press release issued: 6 March 2015

Thyroid hormones have important and diverse roles in human health and regulate metabolic rate. Thyroid disease is common (affecting 5-10 per cent of the population) and synthetic thyroid hormones are one of the commonest drug therapies prescribed worldwide. A new study, published in Nature Communications involving University of Bristol academics, reports a new gene called SYN2 associated with thyroid levels.

Researchers found the SYN2 gene plays an important role in the control of thyroid stimulating hormone. The study also reports a separate, rare, genetic variant present in only four individuals per 1,000 people that can cause thyroxine levels in the blood to be elevated. Although thyroid hormones are essential for childhood development and maintaining adult health, the genetic control of these important hormones is poorly understood.

Data collected from around 4,000 people in the UK and cohorts in Europe and Australia enabled scientists to discover genes and mechanisms affecting the thyroid.

Dr Peter Taylor from the Institute of Molecular and Experimental Medicine at Cardiff University, said: “Thanks to the detailed genetic data available through a whole genome sequencing study, the UK10K project, we identified rare variants associated with thyroid hormone levels which could not have been detected in earlier studies.”

The whole genomes which formed the basis of the study come from two important groups of people who have been studied for many years - the TwinsUK Adult Twin Registry and probably the most well studied adults in the world, and the University of Bristol’s ALSPAC (Avon Longitudinal Study of Parents and Children) studies. The data for each group include extensive descriptions of their health and their development. Additional participants were from Busselton, Australia and Sardinia and Val Borbera, Italy.

Professor Scott Wilson, the study’s lead author, said: “This whole genome sequence data has enabled us to identify that both common genetic variants with modest effects and rarer genetic variants with larger effects determine an individual’s thyroid status.”

Professor Tim Spector, who leads the TwinsUK study at King's College London said, "We are fortunate to have such excellent collections of clinical research material provided by altruistic volunteers to help in medical research.” More than 16,000 volunteers have contributed to this research across several countries. The base data comes from the largest genome-sequencing project so far completed. “It's humbling to see the generosity of participants in these studies. The success comes from combining the largest genome sequencing projects performed to date with the most well characterised population samples in the world.”

This is one of the first in a series of UK10K studies using whole genome sequence data and clinical information to identify genetic variants which influence health right across the frequency spectrum

Dr Nicholas Timpson, one of the co-authors from the Medical Research Council (MRC) Integrative Epidemiology Unit at the University of Bristol 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 endeavour and we are now beginning to realise its potential."

Abstract, full paper and PDF available here:

If you cannot manage anything else, read the Conclusion.


15 Replies

  • Thanks for this Rod most of the txt was lost in me so I appreciate you giving us the gist.

    All the women since my grandma on my maternal side bar one aunt who died young have/had some problem with their thyroid so perhaps these genes are relevant in our case.

  • 'The Seven Daughters of Eve - a book written by Brian Sykes - explains about mitochondrial DNA passing down through the females - hence the book title. Have just re-read it :-)

  • Thanks Marz - sounds a very interesting book. I know they can trace us back to one woman through DNA :-) but I have no idea of the machinations to get there guess the Sykes book explains all that.

  • Yes it does. There are 7 tribes he isolated - and he gave the 7 women names. Just throughout Europe and the near middle east. It is a good read as it wasn't until they discovered the mitochondrial DNA that they could prove the Polynesians came down from Taiwan and not across the sea from S America - as in Kon-Tiki and Thor Heyerdhal :-) Through the website Oxford Ancestors you can have your DNA tested I believe. As with medical research being published - he too had a hard time getting his work out there as he was going against the tide of the current great thinkers :-(

  • I must try and read it, although that could be quite a challenge! I find reading more than sound bites very hard going, yet I devoured dry technical tomes like there was no tomorrow before hypo took hold! I should see if I have got any better at reading more involved stuff since taking NDT!

  • Its more of a story really - so nothing too heavy - otherwise I wouldn't get through it either :-)

  • Is that where you have a gene that does not allow proper conversion from T4 to T3, Sandy12? I had better look it up! Ta

  • No. It is where even when you have what would otherwise be perfectly reasonable levels of thyroid hormones in your blood, your cells do not get enough. The exact mechanisms are not properly understood but you can think of it as if the cell membranes do not transport it from outside the cell to the inside. You can be awash with thyroid hormone but still effectively be hypothyroid.

    Also, and perhaps preferably, called Reduced Sensitivity to Thyroid Hormone. If you want to know more, prepare yourself for a chapter of Thyroid Manager:


  • Thanks Rod. Will read it later.

  • Thanks Rod.

    Am I right in thinking this statement means that population TSH and FT4 ranges are inappropriate because the may include rare genetic variants which skew the ranges?

    Studies including individuals with subclinical thyroid disease, particularly those who are negative for thyroid autoantibodies, may be particularly rewarding, as rare genetic variants with large effect sizes may be associated with serum TSH and FT4 concentrations outside the inclusion ranges we used and therefore would not be detected in our analyses.

    I hope the conclusion that borderline TSH levels may be due to genetic variation doesn't discourage treatment for symptomatic sub clinical patients but applaud further investigation of TSH differences in the population.

    Such endeavours are clinically relevant, as there has been a dramatic increase in ​levothyroxine prescribing for borderline TSH levels29. At least three loci identified in this study show evidence of responsiveness to ​levothyroxine in cell line models, underscoring that borderline TSH levels often reflect the influence of genetic variation rather than overt autoimmune thyroid disease, in which case thyroid hormone replacement may not be appropriate. Our results indicate that further investigation of TSH heterogeneity at the population level is necessary.

    I wonder how many years it will be before personalised genome sequencing is commonplace?

  • Yes I wondered about the sub clinical treatment being withdrawn based on the bit you quote. What are you supposed to do if you have one of these genes messing things up, I wonder? Roll on personalised treatment based on ones genome rather than the blunt instrument of TSH testing. Guess I will have long cocked up my toes by then, but who knows?

  • That also concerns me. i mean there are people with TSH 5 and they feel great. But....

  • I felt ghastly at 6.3 and not much better till it was <0.25. It is incredible to me that 5 suits some people do they really exist?

  • Thanks very much for this Rod, very interesting. I was chosen to take part in UK Biobank and I know there is a lot of research ongoing from that. I have had q's relating to my diet (GF and lacto free) hubby is going for scans which I think is a project to llok at arteries/veins/aneurisms. I was reading yesterday about 23 and me and the info that you can get from the if you send a DNA sample. I think in the future we will all get our DNA checked so that we can have treatmetn/advice that will pre empt ill health. That will be a novelty, pre-emptive health care insted of reactive!

  • Hmmm. I wish. But apparently epigenetics (what happens to you after birth) is more important than the genes you were born with - nurture, not nature. What it will actually mean that is anyone with a "dodgy" gene will be unable to get travel health insurance, will probably have to pay extra for health care and will be bullied into unnecessary treatment (I bet they find a gene for depression) - a bit like living in a postcode that has had floods, even when your street has never, ever flooded.

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