A LD block of 23 SNPs in the XPA/FOXE1 (TTF-2) region was highly associated with fasting serum TSH (MAF = 0.25-0.29, effect size = 2.9-3.8%). The association is likely attributed to FOXE1 rather than XPA which is involved in DNA excision repair [40] and the skin disease xeroderma pigmentosum [41]. FOXE1 or thyroid transcription factor 2 (TTF-2) belongs to the ‘forkhead’ gene family and is involved in promoting the migration process or in repressing differentiation of the thyroid follicular cells until migration has occurred [42] and has been associated with thyroid cancer [43]–[46]. In the Kosrae population, plasma TSH levels were strongly associated with 10 SNPs in a region encompassing TTF-2 on chromosome 9 [38]. In a cohort of Caucasian adults, genetic variation in FOXE1(TTF-2) showed significant effects on free T4 levels and borderline effects on serum TSH [47]. Three of the SNPs (rs925488, rs1877431, rs1588635) detected in the VIVA cohort was also reported by Lowe et.al (38); there was no overlap with Medici et al (43). Also, three of the SNPs (rs2805809, rs2668804, rs2808693) reported by Lowe et al.
