One of the more genetic common cancers, and two studies from the same group both point the same way: the loci that raise risk also lower thyroid-stimulating hormone, and the strongest one sits on the gene that builds the thyroid gland in the embryo.
The thyroid is a small gland at the base of the neck that makes hormones — thyroxine (T4) and triiodothyronine (T3) — that set the pace of metabolism throughout the body. It is controlled by thyroid-stimulating hormone (TSH) from the pituitary gland, in a feedback loop: more thyroid hormone, less TSH, and back again.
Thyroid cancer is, among common cancers, unusually genetic — twin and family studies put its heritability among the highest of any cancer studied this way — which is what made it a productive target for genome-wide scanning early.
Both papers behind this page came from the same Icelandic group. The first, in 2009, scanned thyroid cancer directly: 192 Icelandic cases against 37,196 controls, with replication in further European populations. It found two loci — one on 9q22.33, near FOXE1, with an odds ratio of 1.75; and one on 14q13.3, near NKX2-1, with an odds ratio of 1.37. Both risk alleles were also associated with lower TSH in the general population.
The second paper, in 2012, came at the same territory from the other direction. Rather than scanning cancer, it scanned TSH levels in 27,758 Icelanders, then tested the loci that moved TSH against thyroid cancer case-control data. Three were confirmed, and one of them was in the same 14q13.3 region the 2009 paper had already found — a second, uncorrelated variant there, with an odds ratio of 2.09, the largest effect on this page. A second locus, on 8p12, sits near NRG1 — neuregulin 1, a signalling protein — and showed a very strong association with NRG1's own expression level in blood.
Two independent designs, five years apart, converging on the same region and the same relationship to TSH is the kind of agreement genetics does not produce by chance. NKX2-1 (also called TTF1) is a transcription factor required for the thyroid gland to form during embryonic development, and it stays active in thyroid follicular cells — the hormone-producing cells — for life. A locus near the gene that builds the thyroid follicular cell, shifting both the hormone that drives that cell and the cell's own cancer risk, is a coherent biological story rather than a coincidental one.
This site's strongest single locus from the 2009 paper — 9q22.33, near FOXE1, odds ratio 1.75 — is not on this page. The collector recorded a different marker in the neighbouring 14q13.3 region instead. The page says so rather than implying the strongest finding is represented here.
Positions joined since this page was written
What this is The text above discusses the variants this page was written around. Since then the catalogue has joined 28 more positions to it, by shared trait or shared paper. They are listed here by the paper each came from; the text does not describe them, and each variant page carries that study's own record.
Jee YH et al. 2026, Nature communications rs143459581 (TTC28), rs17767904 (MAFTRR), rs4733129 (NRG1), rs11245983 (BET1L), rs17089782 (PIBF1), rs1979221 (near LINC02964), rs3744962 (ENOSF1), rs189000246 (near SORCS3), rs115317600 (near RNU6-660P), rs34152346 (EIF4ENIF1), rs116531088 (near RN7SL167P), rs74341405 (KIF15) and 1 more — PMID:42431967
White SL et al. 2026, Nature genetics rs4804433 (INSR), rs145702999 (TERF1), rs16977564 (CGNL1), rs558620854 (THEM7P), rs748832306 (SHD), rs559797352 (EHMT1) — PMID:41644669
Verma A et al. 2024, Science (New York, N.Y.) rs8020481 (LINC00609), rs537876632 (ZNF765), rs142700723 (LINC00861), rs191643749 (near ANKRD44) — PMID:39024449
Sakaue S et al. 2021, Nature genetics rs9642727 (NRG1) — PMID:34594039
Feng X et al. 2022, JAMA network open rs2618148 (DIRC3) — PMID:36508215
Gudmundsson J et al. 2017, Nature communications rs12129938 (PCNXL2) — PMID:28195142
Choe EK et al. 2022, Scientific reports rs149128637 (near TMEM100) — PMID:35121771
Son HY et al. 2017, Nature communications rs9858271 (FHIT) — PMID:28703219
2026-07-10 · Jee YH, et al. Nature Communications 2026, PMID:42431967
Genetic drivers of etiologic heterogeneity in thyroid cancer
Newly curated by the GWAS Catalog: 66 associations across 1 trait ("Thyroid cancer"), from Jee YH, et al. in Nature Communications, 2026. The catalogue records its sample as 10,717 cases and 1,262,106 controls. This site already has 22 of its 66 positions — 13 on the Thyroid Cancer page; 2 on the Ovarian Cancer page; 2 on the Blood Cell Counts page — including rs4733129 (NRG1), rs116909374 (MBIP), rs10069690 (TERT). Everything above is from the catalogue's records, assembled by code; the paper itself is linked. PMID:42431967.
2026-02-26 · Genome-wide association analyses of autoimmune hypothyroidism reveal autoimmune and thyroid-specific contributions and an inverse relationship with cancer risk. Nature Genetics. 2026. DOI:10.1038/s41588-026-02521-1
418 genetic signals for autoimmune hypothyroidism, and a surprising inverse link to cancer risk
Autoimmune hypothyroidism (AIHT) affects over 5% of people, making it common enough to cleanly separate general-autoimmunity genetics from thyroid-specific genetics. This meta-analysis of 81,718 AIHT cases in FinnGen and UK Biobank found 418 independent genome-wide significant signals -- a massive genetic map for a single condition. At 48 loci, the lead variant was itself a protein-coding change, including Finnish-enriched coding variants in LAG3, ZAP70 and TG; the study demonstrated experimentally that the ZAP70:T155M variant reduces T-cell activation. Using a Bayesian classifier comparing AIHT loci against nonthyroid autoimmune disease and TSH-level GWAS, the study estimated 38% of loci reflect general autoimmunity and 20% are thyroid-specific -- a genuine mechanistic split. It also found a striking inverse genetic relationship between AIHT and cancer risk broadly, an unexpected finding warranting its own follow-up. This site's autoimmune thyroid disease page carries just 1 variant and its thyroid cancer page 5; this study is a major addition to both, and the cancer-inverse finding is a direct, genuine link between the two pages.
All three variants here shift risk by a fraction, in a population that already has a wide range of thyroid cancer risk from other causes — the most established of which is radiation exposure, especially in childhood. None of them diagnoses the disease or predicts an individual case.
What actually gets thyroid cancer found. A lump or swelling in the neck, often noticed by the person themselves or found on an examination for something else, is what leads to an ultrasound and, if needed, a fine-needle biopsy. Most thyroid nodules are not cancer. Nothing on this page detects the disease and nothing here should delay that evaluation.
Both risk loci associate with lower TSH in the general population — which, given the feedback loop between the pituitary and the thyroid, points toward a thyroid gland working slightly differently from the start, rather than TSH itself being the cause. This is a mechanistic clue for researchers, not a screening signal: a normal TSH blood test does not rule out thyroid cancer, and TSH testing is not used to assess this genetic risk.
What a 23andMe/AncestryDNA export or raw VCF can and can't tell you about Thyroid Cancer comes down to these specific, well-studied positions — not a diagnosis. 80 positions are linked to this page; the ones this page's own text discusses are shown first.
The studies behind these variants recruited participants from different ancestries — a result found in one population doesn't always transfer to another. Based on 6 of 80 linked studies with a resolved discovery ancestry.
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Thyroid Cancer. MyGeneLog™. https://www.mygenelog.com/conditions/thyroid-cancer
No. The variants here each shift risk by a fraction and none of them detects the disease. A lump or nodule found on examination, followed by ultrasound and often a biopsy, is what actually finds thyroid cancer.
No. The genetic loci here associate with lower average TSH across a population, which is a research clue about mechanism, not something used to assess an individual's cancer risk. TSH testing and thyroid cancer risk are not the same thing.
Because two different starting points — scanning cancer directly, and separately scanning TSH levels — converged on 14q13.3, near NKX2-1, a gene required to build the thyroid gland in the embryo and active in thyroid cells for life. Agreement like that across independent designs is what makes a genetic finding believable.
Radiation exposure, especially in childhood, is a far larger and better-established risk factor for thyroid cancer than anything on this page. If that applies to you, the useful step is discussing surveillance with a doctor, not a genotype.
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