rs7850258

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. 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). 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. 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). 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.