Thyrotoxicosis
diseaseOn this page
Also known as Graves disease, susceptibility to, 1GRD1
Summary
Thyrotoxicosis (MONDO:0010138) is a disease with 53 GWAS associations across 24 studies and 8 clinical trials. Top therapeutic interventions include thiamine ion and corticorelin. A subtype of hyperthyroidism — broader associated-gene and molecular evidence is on the parent page (see Disease family below).
At a glance
- GWAS associations: 53
- Clinical trials: 8
Clinical features
No curated clinical features (Orphanet) for this disease.
Identifiers
Disease identifiers
| Field | Value |
|---|---|
| Canonical name | thyrotoxicosis |
| Mondo ID | MONDO:0010138 |
| EFO | EFO:0009190 |
| MeSH | D013971 |
| DOID | DOID:7997 |
| ICD-10-CM | E05 |
| ICD-11 | 1470387017 |
| NCIT | C61469 |
| SNOMED CT | 90739004 |
| UMLS | C0040156 |
| MedGen | 11814 |
| Is cancer (heuristic) | no |
Also known as: Graves disease, susceptibility to, 1 · GRD1
Data availability: 53 GWAS associations (24 studies).
Disease family
This is a subtype of hyperthyroidism. Genetic, therapeutic, and trial evidence is largely curated at the broader-term level — see the parent page for the associated-gene cohort and molecular evidence.
Classification path: disease › human disease › disease by body system or component › endocrine system disorder › thyroid gland disorder › hyperthyroidism › thyrotoxicosis
Related subtypes (9): toxic diffuse goiter, thyroid crisis, selective pituitary resistance to thyroid hormone, generalized resistance to thyroid hormone, familial gestational hyperthyroidism, familial hyperthyroidism due to mutations in TSH receptor, hyperthyroxinemia, familial dysalbuminemic, primary hyperthyroidism, secondary hyperthyroidism
Subtypes (1): neonatal thyrotoxicosis
Genetics & variants
GWAS landscape
53 GWAS associations across 24 studies. Top hits map to 13 distinct genes (as reported by GWAS).
Top associations by p-value
| rsID | p-value | Gene | Risk allele | Odds ratio |
|---|---|---|---|---|
| chr6:32633960 | 5e-147 | AG | 0.51 | |
| chr14:80990913 | 5e-54 | C | 0.25 | |
| chr2:203874196 | 3e-35 | A | 0.2 | |
| rs9268791 | 1e-34 | HLA-DRA - HLA-DRB9 | ? | |
| rs10799824 | 2e-29 | MICOS10 | G | 0.22 |
| rs9272445 | 6e-27 | HLA-DQA1 | C | 0.57 |
| rs6885099 | 1e-23 | PDE8B | A | 0.17 |
| chr1:113761186 | 1e-23 | A | 0.25 | |
| rs73575085 | 8e-23 | LINC01229, MAFTRR | G | 0.17 |
| chr1:19836221 | 4e-22 | C | 0.26 | |
| rs58266067 | 2e-21 | TSHR | T | 0.16 |
| rs78775620 | 6e-20 | TG | C | 0.51 |
| chr14:81449534 | 1e-19 | T | 0.18 | |
| rs334706 | 6e-19 | NFIA | G | 0.25 |
| rs73398264 | 2e-18 | FAM227B | T | 0.16 |
| rs3087243 | 3e-18 | CTLA4 - ICOS | G | 0.14 |
| chr5:76531648 | 5e-17 | C | 0.17 | |
| chr10:6056861 | 2e-16 | C | 0.13 | |
| chr11:95578258 | 8e-16 | C | 0.17 | |
| chr16:79753976 | 1e-15 | C | 0.16 | |
| chr8:32406549 | 3e-15 | G | 0.18 | |
| rs753760 | 2e-14 | PDE10A | C | 0.13 |
| rs10223666 | 3e-14 | VEGFA - LINC02537 | G | 0.13 |
| rs7825175 | 3e-14 | NRG1 | G | 0.15 |
| chr15:49399084 | 5e-14 | C | 0.14 | |
| chr16:79719674 | 5e-14 | G | 0.13 | |
| rs3758723 | 2e-13 | PRDM11 | T | 0.13 |
| rs13020935 | 3e-12 | TESHL | G | 0.12 |
| chr1:19508012 | 3e-12 | T | 0.15 | |
| chr6:166050119 | 1e-11 | A | 0.14 |
Top studies (by case count)
| Study | Lead author | Year | Cases | Controls | Title |
|---|---|---|---|---|---|
| GCST90473161 | UK Biobank Whole-Genome Sequencing Consortium | 2025 | 7,956 | 450,484 | Whole-genome sequencing of 490,640 UK Biobank participants. |
| GCST90667836 | UK Biobank Whole-Genome Sequencing Consortium | 2025 | 7,956 | 450,484 | Whole-genome sequencing of 490,640 UK Biobank participants. |
| GCST90475643 | Verma A | 2024 | 5,526 | 441,420 | Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program. |
| GCST90651161 | Liu TY | 2025 | 5,056 | 212,391 | Diversity and longitudinal records: Genetic architecture of disease associations and polygenic risk in the Taiwanese Han population. |
| GCST90077728 | Backman JD | 2021 | 3,510 | 328,244 | Exome sequencing and analysis of 454,787 UK Biobank participants. |
| GCST90081714 | Backman JD | 2021 | 3,510 | 328,244 | Exome sequencing and analysis of 454,787 UK Biobank participants. |
| GCST90079730 | Backman JD | 2021 | 3,102 | 383,241 | Exome sequencing and analysis of 454,787 UK Biobank participants. |
| GCST90083716 | Backman JD | 2021 | 3,102 | 383,241 | Exome sequencing and analysis of 454,787 UK Biobank participants. |
| GCST90077729 | Backman JD | 2021 | 2,796 | 326,256 | Exome sequencing and analysis of 454,787 UK Biobank participants. |
| GCST90081715 | Backman JD | 2021 | 2,796 | 326,256 | Exome sequencing and analysis of 454,787 UK Biobank participants. |
Variant details and genetic-evidence tiers
Tier distribution (top 50 variants)
| Tier | Variants |
|---|---|
| Tier 1: coding | 0 |
| Tier 2: splice/UTR | 0 |
| Tier 3: regulatory | 0 |
| Tier 4: intronic/intergenic | 49 |
MAF distribution
| Bucket | Variants |
|---|---|
| common (>=0.05) | 22 |
| low_freq (0.01-0.05) | 1 |
| rare (<0.01) | 0 |
| unknown | 26 |
Functional consequences
| Consequence | Count |
|---|---|
| unknown | 34 |
| intron_variant | 14 |
| intergenic_variant | 1 |
Top variants
| rsID | Chr | Pos | Alleles | MAF | Consequence | Gene | p-value | Tier |
|---|---|---|---|---|---|---|---|---|
| chr6:32633960 | 5e-147 | Tier 4: intronic/intergenic | ||||||
| chr14:80990913 | 5e-54 | Tier 4: intronic/intergenic | ||||||
| chr2:203874196 | 3e-35 | Tier 4: intronic/intergenic | ||||||
| rs9268791 | 6 | 32453296 | T>A,C,G | 0.05 | intron_variant | HLA-DRA - HLA-DRB9 | 1e-34 | Tier 4: intronic/intergenic |
| rs10799824 | 1 | 19514680 | G>A | 0.167 | intron_variant | MICOS10 | 2e-29 | Tier 4: intronic/intergenic |
| rs9272445 | 6 | 32637643 | C>A,T | 0.076 | intron_variant | HLA-DQA1 | 6e-27 | Tier 4: intronic/intergenic |
| rs6885099 | 5 | 77234524 | A>C,G,T | 0.462 | intron_variant | PDE8B | 1e-23 | Tier 4: intronic/intergenic |
| chr1:113761186 | 1e-23 | Tier 4: intronic/intergenic | ||||||
| rs73575085 | 16 | 79714179 | G>C | 0.296 | intron_variant | LINC01229, MAFTRR | 8e-23 | Tier 4: intronic/intergenic |
| chr1:19836221 | 0.148 | 4e-22 | Tier 4: intronic/intergenic | |||||
| rs58266067 | 14 | 81002132 | T>A,C | 0.339 | intron_variant | TSHR | 2e-21 | Tier 4: intronic/intergenic |
| rs78775620 | 8 | 132869226 | C>T | 0.019 | intron_variant | TG | 6e-20 | Tier 4: intronic/intergenic |
| chr14:81449534 | 0.397 | 1e-19 | Tier 4: intronic/intergenic | |||||
| rs334706 | 1 | 61150575 | G>A,C | 0.086 | intron_variant | NFIA | 6e-19 | Tier 4: intronic/intergenic |
| rs73398264 | 15 | 49414220 | T>C | 0.22 | intron_variant | FAM227B | 2e-18 | Tier 4: intronic/intergenic |
| rs3087243 | 2 | 203874196 | G>A,T | 0.403 | intergenic_variant | CTLA4 - ICOS | 3e-18 | Tier 4: intronic/intergenic |
| chr5:76531648 | 0.383 | 5e-17 | Tier 4: intronic/intergenic | |||||
| chr10:6056861 | 2e-16 | Tier 4: intronic/intergenic | ||||||
| chr11:95578258 | 8e-16 | Tier 4: intronic/intergenic | ||||||
| chr16:79753976 | 0.313 | 1e-15 | Tier 4: intronic/intergenic | |||||
| chr8:32406549 | 0.201 | 3e-15 | Tier 4: intronic/intergenic | |||||
| rs753760 | 6 | 165632995 | C>A,G,T | 0.317 | intron_variant | PDE10A | 2e-14 | Tier 4: intronic/intergenic |
| rs10223666 | 6 | 43837765 | G>A,C,T | 0.302 | intron_variant | VEGFA - LINC02537 | 3e-14 | Tier 4: intronic/intergenic |
| rs7825175 | 8 | 32558756 | G>A,C | 0.18 | intron_variant | NRG1 | 3e-14 | Tier 4: intronic/intergenic |
| chr15:49399084 | 5e-14 | Tier 4: intronic/intergenic | ||||||
| chr16:79719674 | 5e-14 | Tier 4: intronic/intergenic | ||||||
| rs3758723 | 11 | 45221961 | T>C | 0.252 | intron_variant | PRDM11 | 2e-13 | Tier 4: intronic/intergenic |
| rs13020935 | 2 | 216760956 | G>A,C,T | 0.334 | intron_variant | TESHL | 3e-12 | Tier 4: intronic/intergenic |
| chr1:19508012 | 3e-12 | Tier 4: intronic/intergenic | ||||||
| chr6:166050119 | 0.321 | 1e-11 | Tier 4: intronic/intergenic |
Genes & proteins
No associated-gene cohort resolved for this disease. Atlas builds the molecular and therapeutic sections — associated genes, protein families, druggability, pathways, interactions, and drug associations — by aggregating over a disease’s associated genes (resolved via GWAS / GenCC / ClinVar / CIViC), and none resolved here. This is expected for antibody-mediated, autoimmune, or otherwise non-gene-defined conditions; the curated evidence for this disease is its clinical features, GWAS susceptibility, and clinical trials (above).
Function
No pathway enrichment — requires an associated-gene cohort.
Therapeutics
Drugs indicated for this disease
0 approved, 2 in late-stage (phase 3) trials. Disease-direct ChEMBL indications, not inferred from the associated-gene cohort below.
| Drug | Development status |
|---|---|
| Carbimazole | Phase 3 (in late-stage trials) |
| Propylthiouracil | Phase 3 (in late-stage trials) |
Clinical trials & evidence
Clinical trials
Clinical trials: 8.
Phase distribution (across all retrieved trials)
| Phase | Trials |
|---|---|
| Not specified | 8 |
Top trials by phase / activity
| NCT | Phase | Status | Title |
|---|---|---|---|
| NCT06264544 | Not specified | NOT_YET_RECRUITING | Trial to Evaluate the Efficacy of a Zinc, Selenium, and L-Tyrosine Supplement in the Prevention of Thyrotoxicosis in Subjects With r25191G/A SEPP1 Polymorphism |
| NCT01227499 | Not specified | COMPLETED | Differential Diagnosis of STA-PSV in Thyrotoxicosis |
| NCT02767245 | Not specified | COMPLETED | Thiamine Supplement in Patients With Severe Hyperthyroidism |
| NCT02886949 | Not specified | UNKNOWN | The Association Between Autoimmune or Inflammation and Thyroid Disease |
| NCT03009357 | Not specified | COMPLETED | Clinical Application of Pulse Rate-monitoring Activity Trackers in Thyrotoxicosis |
| NCT04485975 | Not specified | COMPLETED | Therapeutic Plasma Exchange in Thyrotoxicosis |
| NCT04806269 | Not specified | UNKNOWN | Biosignals by Wearables in Thyroid Dysfunction |
| NCT06391515 | Not specified | COMPLETED | Subacute Thyroiditis in the SARS-CoV-2 Era |
Drugs tested across these trials (top 30)
| Molecule | Max phase | Trials referencing |
|---|---|---|
| THIAMINE ION | 4 | 2 |
| CORTICORELIN | 3 | 1 |
Related Atlas pages
- Drugs: Thiamine Ion, Corticorelin