Hypothyroidism
An underactive thyroid, whose genetic risk spans two different kinds of biology at once — autoimmune loci shared with many other immune diseases, and genes directly involved in making and regulating thyroid hormone.
What this condition connects to
Hypothyroidism — an underactive thyroid gland, producing too little thyroid hormone — is the most common thyroid disorder, affecting roughly 5% of the general population. This page holds 211 variants from three genetic studies. This site has separate pages for autoimmune thyroid disease (Graves' and Hashimoto's specifically), TPO antibodies (the autoimmune marker), and thyroid cancer; this page is about hypothyroidism itself as a clinical outcome, a distinct GWAS trait from all three.
Two different kinds of genetic risk, in the same disease
A 2012 study of 3,736 people with hypothyroidism and 35,546 without (diagnosis via web-based questionnaire) found five genome-wide-significant loci, and reported something specific about their mix: three of them — PTPN22, SH2B3, and the HLA class I region (the source of this page's rs2517532) — were already known risk factors across a broad spectrum of unrelated autoimmune diseases, while the other two, VAV3 and FOXE1, were newly reported for hypothyroidism specifically. The study's own conclusion is that this points to real heterogeneity in what causes hypothyroidism — some of it autoimmune in origin, some of it tied more directly to thyroid function itself.
A larger, later study: 109 loci across thyroid function and dysfunction
A 2018 meta-analysis tested 8 million genetic variants in up to 72,167 people across the full spectrum of thyroid function and dysfunction traits, identifying 109 independent associated variants in total. Its functional follow-up work singled out two genes as newly characterized — SLC17A4, a thyroid hormone transporter, and AADAT, a thyroid-hormone-metabolizing enzyme — neither of which is among this page's four variants from that study (CAPZB, TPO, PDE10A, FMNL1). Those four come from the same genome-wide-significant result set, without the same individual mechanistic follow-up. TPO, independently of this study, is well established as the gene for thyroid peroxidase, the enzyme that synthesizes thyroid hormone — a different question from the anti-TPO antibody this site's TPO-antibodies page covers, which shares no rsID or specific finding with this page.
A 2026 study added 206 more, at far larger scale
A 2026 meta-analysis studying five thyroid diseases together across 19 biobanks (also the basis of this site's new benign nodular goiter page) contributed 206 more of this page's variants — by far the majority of what is here. Among them is TSHR, the thyroid-stimulating hormone receptor itself, the protein TSH binds to trigger thyroid hormone production — about as directly relevant to hypothyroidism as a gene can be. Alongside it sits a long list of immune-regulation genes already familiar from other autoimmune-disease GWAS on this site, including IL2RB, CD226, CD6, TBX21, RASGRP1 and NKX2-3. At far larger scale than the founding 2012 study could manage, this extends the same two-track pattern that study first proposed: some of hypothyroidism's genetics sits squarely in thyroid-hormone biology, and a separate, substantial share sits in general immune regulation shared with unrelated autoimmune diseases.
In the news
2026-07-29 · Nature Genetics
Largest Hashimoto's thyroiditis genetics study finds 19 new risk regions
A multi-ancestry meta-analysis of 48,694 people with Hashimoto's thyroiditis and 1,044,134 controls found 155 independent genetic associations, of which 45 variants across 19 loci had never been linked to hypothyroidism before. Functional analysis pointed at immune cells and the spleen specifically, underscoring T cells' role in the disease, supported by 161 significant links to gene-expression changes in immune cells and 40 in thyroid tissue itself. Six loci were specific to European-ancestry populations, highlighting real ancestry-specific genetic architecture alongside the shared signal. PMID:42527560.
2026-02-19 · Schmidt A, et al., Nature 2026, PMID:41714741
Host control of persistent Epstein-Barr virus infection
Epstein-Barr virus infects roughly 90-95% of people and stays for life in B cells. This study read EBV out of ordinary blood-based genome sequencing: EBV reads turned up in 16.2% of 486,315 UK Biobank participants and 21.8% of 336,123 All of Us participants, tracking higher viral load in blood cells, and were more common with HIV infection, immunosuppressive drugs and current smoking. Genome-wide, the strongest signals were in the MHC — 54 independent HLA alleles across classes I and II — plus 27 regions outside it, with an interaction between HLA class I alleles and the ERAP2 locus. People with EBV-associated diseases carried a higher polygenic burden of the EBV-positive signal: at MHC class I in multiple sclerosis (driven by HLA-A*02:01) and at MHC class II in rheumatoid arthritis, with polygenic overlap also seen for inflammatory bowel disease, hypothyroidism and type 1 diabetes. Four of the study's non-MHC positions are already on this site — rs13098877 (LPP), rs884186 (KSR1), rs9828869 (near ILDR1) and rs34557412 (TNFRSF13B) — the last also linked here to lymphocyte count. PMID:41714741.
From our blog
Clinical detail
What is actually diagnosed and treated here
Hypothyroidism is diagnosed by blood tests (TSH and free T4 levels), not by genotype. None of the 211 variants on this page are used by any guideline to diagnose hypothyroidism or predict who will develop it.
The loci described above come from population-level genetic studies of thousands to tens of thousands of people. The 2012 study's own genetic-risk-profile score, built from its five loci, found only a 2-fold difference in relative risk between the highest and lowest deciles — useful for describing population-level heterogeneity in cause, far too small a signal to predict an individual's risk.
Related variants MyGeneLog™ checks for
What a 23andMe/AncestryDNA export or raw VCF can and can't tell you about Hypothyroidism comes down to these specific, well-studied positions — not a diagnosis. 249 positions are linked to this page; the ones this page's own text discusses are shown first.
Which ancestries this evidence comes from
The studies behind these variants recruited participants from different ancestries — a result found in one population doesn't always transfer to another. Based on 12 of 249 linked studies with a resolved discovery ancestry.
Sources
Databases, guidelines and references
Quoting this page
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Hypothyroidism. MyGeneLog™. https://www.mygenelog.com/conditions/hypothyroidism
Questions about Hypothyroidism
What is hypothyroidism?
An underactive thyroid gland that produces too little thyroid hormone. It is the most common thyroid disorder, affecting roughly 5% of the general population.
Is hypothyroidism always autoimmune?
No. The founding genetic study of hypothyroidism found its five known risk loci split between genes already linked to autoimmune disease broadly and genes tied more directly to thyroid function itself — evidence of real heterogeneity in what causes it, not one single cause.
Is this the same as the TPO-antibody page on this site?
No. This page covers hypothyroidism as a clinical outcome; the separate TPO-antibodies page covers the autoimmune antibody marker. They share no rsID or specific finding between them, even though this page includes a variant in the TPO gene itself (the thyroid hormone-synthesizing enzyme, a different question from the antibody against it).
Can these variants predict whether I will get hypothyroidism?
No. Hypothyroidism is diagnosed by blood tests (TSH and free T4), not genotype. A genetic risk score built from this page's founding study found only a 2-fold difference in relative risk between the highest and lowest risk deciles — not enough to predict an individual case.
What did the 2026 thyroid study add to this page?
206 more variants, the large majority of what this page now holds -- including TSHR, the thyroid-stimulating hormone receptor gene itself, and a long list of immune-regulation genes (IL2RB, CD226, CD6, TBX21, RASGRP1, NKX2-3 among others) that extend, at far larger scale, the same autoimmune-versus-thyroid-function split the founding 2012 study first proposed.
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