Graves' disease and Hashimoto's thyroiditis look like opposites clinically — one over-active, one under-active — but a 2012 study found genetic risk they share, including one locus also linked to celiac disease.
Autoimmune thyroid disease (AITD) covers two conditions that look clinically opposite — Graves' disease (an over-active thyroid) and Hashimoto's thyroiditis (an under-active one) — but share an immune-mediated cause. This site has a separate page for Graves' disease's own MHC-region findings and for the TPO antibody that marks autoimmune thyroid activity; this page is about a different kind of finding — a risk locus shared across both diseases, outside the MHC.
Cooper et al. 2012 used a dense genotyping array (Immunochip) to study 2,285 people with Graves' disease and 462 with Hashimoto's thyroiditis against 9,364 controls, and found 7 new AITD risk loci. One of them is rs13093110, near LPP: an odds ratio of 1.18 in the Graves' cohort alone, 1.20 in the Hashimoto's cohort alone, and 1.19 combined (p=3.69×10⁻⁸) — a real example of a locus that raises risk for both diseases rather than one specifically.
rs13093110 is in near-complete linkage disequilibrium with rs1464510, a variant already reported in celiac disease — a gut, not thyroid, autoimmune condition. Shared genetic risk across unrelated-looking autoimmune diseases is a recurring pattern in this field, and the paper is candid about what is and is not understood here: LPP itself has an "uncertain or unknown" role in autoimmunity, unlike BACH2 (a known regulator of antiviral immune responses), another of the study's 7 new loci.
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.
Graves' disease and Hashimoto's thyroiditis are diagnosed by thyroid hormone and antibody blood tests, not by genotype. The variant on this page is not used by any guideline to diagnose either condition or predict which one a person will develop.
The odds ratios above (around 1.2) are modest, population-level effects from a study of thousands of people — not an individual risk prediction, and not a reason to test for or act on this variant clinically.
What a 23andMe/AncestryDNA export or raw VCF can and can't tell you about Autoimmune Thyroid Disease comes down to these specific, well-studied positions — not a diagnosis.
LPP · rs13093110
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Autoimmune thyroid disease covers Graves' disease (an over-active thyroid) and Hashimoto's thyroiditis (an under-active one) — clinically opposite, but sharing an immune-mediated cause.
Studying 2,285 people with Graves' disease and 462 with Hashimoto's thyroiditis against 9,364 controls, it found 7 new risk loci — including rs13093110 near LPP, which raises risk of both diseases rather than one specifically.
Yes. rs13093110 is in near-complete linkage disequilibrium with a variant already reported in celiac disease, a gut rather than thyroid autoimmune condition — one more example of shared genetic risk across seemingly unrelated autoimmune diseases.
No. Both are diagnosed with thyroid hormone and antibody blood tests, not genotype. The odds ratio here (around 1.2) is a modest, population-level effect, not an individual prediction.
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