|| Slightly lower odds of developing primary hypothyroidism.
|| Typical odds of developing primary hypothyroidism.
|| Slightly higher odds of developing primary hypothyroidism.
|?|| (A;A) (A;G) (G;G) ||28|
|| [PMID 21981779]
|| Variants near FOXE1 are associated with hypothyroidism and other thyroid conditions: using electronic medical records for genome- and phenome-wide studies.
| Risk Allele
| Odds Ratio
|| 1.2300 None
rs7850258 is located on chromosome 9 and is 67 kb from the nearest gene, FOXE1. FOXE1, also known as thyroid transcription factor 2, is an intronless gene with a crucial role in thyroid morphogenesis. This SNP is associated with primary hypothyroidism. [PMID 21981779] Primary hypothyroidism is the most common thyroid disorder, affecting 1-5% of the population, and is characterized by deficiencies of thyroid hormones T3 (triiodothyronine) and T4 (thyroxine). [PMID 22493691]
Using electronic medical record-linked DNA biobanks, a study with 1,317 cases and 5,053 controls of European American ancestry identified rs7850258 to have the strongest association with hypothyroidism. The odds ratio for the minor allele A was 0.74 (p-value = 3.96 x 10-9). This SNP was in strong pair-wise linkage disequilibrium (r2 > 0.98) with three other SNPs 58-71 kb from FOXE1, rs965513, rs925489, and rs10759944. [PMID 21981779]
This association was replicated in a GWAS of 3,736 cases and 35,546 controls with a similar odds ratio of 0.78 (95% confidence interval = 0.74-0.82) for the association of rs7850258 with hypothyroidism. All participants were customers of 23andMe, Inc and of mostly European ancestry. They also found five other variants significantly associated with hypothyroidism near FOXE1 (rs925489), PTPN22 (rs6679677), SH2B3 (rs3184504), VAV3 (rs4915077), and the HLA region (rs2517532). [PMID 22493691]
[PMID 24270849] rs7850258 was found to be associated with hypothyroidism based on a study by the eMERGE network in which electronic medical records were searched to find clinical associations associated with selected SNPs.
[PMID 25652407] A Single Nucleotide Polymorphism Associated with Isolated Cleft Lip and Palate, Thyroid Cancer and Hypothyroidism Alters the Activity of an Oral Epithelium and Thyroid Enhancer Near FOXE1