Autoimmune thyroid disease affects 2–5% of people, and the antibody that marks it is often present years before anything goes wrong. The genetics of having the antibody is not the same question as the genetics of getting ill.
The thyroid is attacked by the immune system more often than almost any other organ. The two named outcomes are opposite in effect: Hashimoto's thyroiditis, where the gland is damaged and underproduces, and Graves' disease, where it is driven and overproduces.
Both are marked by antibodies against thyroid peroxidase — TPO, the enzyme that puts iodine into thyroid hormone. Having those antibodies raises the risk of both.
Autoimmune thyroid disease affects 2–5% of the general population. TPO antibodies are commoner still, and can be present for years in someone whose thyroid is working perfectly well.
That gap is the interesting part. The antibody is a marker of a process that has started, not a diagnosis of a disease that has arrived.
A 2014 meta-analysis did something worth noticing: it treated having the antibody and how much of it you have as different traits, and asked about each.
Both were replicated in a further 8,990. And the two lists overlap in exactly one gene: TPO itself.
Whether your immune system starts making an antibody, and how much it makes once it has started, are apparently not the same trait. Splitting them was a design choice, and it produced two answers where treating it as one question would have produced a blur.
rs10944479 is at BACH2, one of the positivity loci. BACH2 is a transcription factor that governs how B and T cells differentiate — a general switch in adaptive immunity rather than anything thyroid-specific.
It turns up across autoimmune disease: type 1 diabetes, coeliac disease, multiple sclerosis and others. So this is not a thyroid gene that happens to affect immunity. It is an immunity gene whose effect shows up in the thyroid, among other places.
Nothing useful about you. The antibody itself is measured directly with a cheap blood test, and a measurement always beats a prediction — the same argument this site makes about vitamin D and about CRP.
Thyroid function is assessed with TSH and thyroid hormone levels, with antibodies used to establish whether an abnormality is autoimmune in origin. Treatment follows those numbers. No genotype enters any of it.
Source. Medici et al. (PLoS Genet 2014) reported that autoimmune thyroid diseases affect 2–5% of the general population, and that individuals with positive thyroid peroxidase antibodies have increased risk of both autoimmune hypothyroidism (Hashimoto's thyroiditis) and autoimmune hyperthyroidism (Graves' disease). Genome-wide association meta-analyses were performed in 18,297 individuals for TPOAb-positivity (1,769 positive, 16,528 negative) and in 12,353 individuals for TPOAb serum levels, with replication in 8,990 individuals. Significant associations (P < 5 × 10⁻⁸) were detected at TPO-rs11675434, ATXN2-rs653178 and BACH2-rs10944479 for positivity, and at TPO-rs11675434, MAGI3-rs1230666 and KALRN-rs2010099 for antibody levels. Individual and combined effects of these variants on subclinical and overt hypo- and hyperthyroidism, goitre and thyroid cancer were examined.
Position listed here. rs10944479 at BACH2. The other index SNPs named above are not in our variant table.
Two phenotypes. Antibody positivity and antibody concentration were analysed as separate traits and returned overlapping but distinct locus sets, sharing only TPO. Treating them as one phenotype would conflate the propensity to break tolerance with the magnitude of the response once tolerance is broken.
Clinical use. None. TPO antibodies are measured directly by immunoassay; thyroid status is assessed by TSH with free thyroid hormones. Antibody testing is used to attribute a biochemical abnormality to autoimmunity, not to predict it, and no genotype is used in screening, diagnosis or management.
What a 23andMe/AncestryDNA export or raw VCF can and can't tell you about Thyroid Autoimmunity (TPO Antibodies) comes down to these specific, well-studied positions — not a diagnosis.
Not on that basis. TPO antibodies can be present for years in people whose thyroid works perfectly well, and they mark a process that has started rather than a disease that has arrived. What they justify is keeping an eye on thyroid function, which is a conversation with your doctor.
Because the study found they are not the same trait. The two analyses returned different sets of genes, overlapping in only one — TPO itself. Breaking tolerance and mounting a large response once tolerance is broken appear to be partly different things.
No. The antibody is measured directly with a cheap blood test and thyroid function with another, and a measurement beats a prediction. No guideline uses a genotype anywhere in this.
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