A 2015 whole-genome sequencing study found variants in SYN2 and PDE8B linked to TSH levels, the pituitary hormone that regulates the thyroid — common variants together explain at least 20% of how much TSH varies between people.
Solid lines are connections this site curates. Dashed lines mean the two ends share a research paper — worth knowing, and not a claim that one explains the other.
Thyroid stimulating hormone (TSH) is made by the pituitary gland and tells the thyroid how much thyroid hormone to produce. TSH is the single most common blood test used to check thyroid function, precisely because it responds so sensitively to small changes in thyroid hormone levels — it is the standard first screen for both an underactive thyroid (hypothyroidism, where TSH rises) and an overactive one (hyperthyroidism, where TSH falls). TSH levels vary within a wide normal range between healthy people, and part of that variation is genetic.
Taylor et al. 2015 analyzed whole-genome sequence data from the UK10K project (2,287 people), then combined it with further sequence and imputed genotype data across 16,335 people in total, to study the genetics of TSH and a related thyroid hormone, free thyroxine (FT4). For TSH specifically, the study found a novel variant in SYN2 and confirmed an independent signal in PDE8B. This page's rs310763, in SYN2, is that finding (minor allele frequency 23.5%, p=6.15×10⁻⁹). Across TSH and FT4 combined, common variants collectively explain at least 20% of how much these hormone levels vary between people — a meaningful genetic contribution to a trait usually thought of purely in terms of diet, age, and thyroid health.
The study also looked at rarer variants (present in under 1% of people) using a different statistical method built for detecting the combined effect of many rare variants at once, and found a novel association with FT4 (not TSH) in NRG1 — a reminder that common and rare variants can point to entirely different genes even within the same hormone system.
Porcu et al. 2013 ran a separate meta-analysis of both TSH (up to 26,420 people) and FT4 (up to 17,520 people), all with normal thyroid function, and found 26 independent associations in total. Strikingly, the TSH and FT4 signals barely overlapped, despite both hormones being regulated by the same feedback loop between the brain and the thyroid — evidence that different genes shape each hormone's level even when their circulating amounts are tightly linked biologically. Five loci showed clear differences between men and women. Altogether the associated variants explained 5.64% of TSH variance and 2.30% of FT4 variance — and, notably, the TSH loci affected values both within and outside the normal range, hinting at a link to overt thyroid dysfunction as well as everyday variation. Seven of this page's variants come directly from this study's own named loci: SASH1, VEGFA, FGF7, PRDM11, and INSR for TSH, and LHX3 and AADAT for FT4.
TSH is measured directly with a blood test, not estimated from genotype. The variants on this page describe why TSH varies within the normal range between healthy people — they are not used by any guideline to diagnose thyroid disease or to interpret an individual TSH result.
A TSH level outside the normal range is followed up clinically with additional thyroid hormone testing (such as free T4) and, where appropriate, thyroid antibody testing or imaging — not with genetic testing, which has no established role in thyroid function diagnosis or management.
What a 23andMe/AncestryDNA export or raw VCF can and can't tell you about Thyroid Stimulating Hormone (TSH) Levels comes down to these specific, well-studied positions — not a diagnosis. 40 positions are linked to this page; the ones this page's own text discusses are shown first.
Databases, guidelines and references
Thyroid stimulating hormone (TSH) is made by the pituitary gland and tells the thyroid how much thyroid hormone to produce. It is the most common blood test for thyroid function, because it responds sensitively to small changes in thyroid hormone levels.
Analyzing whole-genome sequence data from 2,287 people, then combining it with further data reaching 16,335 people, it found a novel TSH-associated variant in SYN2 and confirmed an independent one in PDE8B. Common variants collectively explain at least 20% of how TSH and a related hormone, FT4, vary between people.
No. These are population-level statistical associations, not individual predictions, and none is used by any guideline to diagnose thyroid disease or interpret a TSH test result. TSH is measured directly with a blood test.
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