Among trait-associated variants with trans-eQTL effects, we found two genome-wide significant trans-eVariants at the 9q22 locus (rs7037324 and rs1867277, R2 = 0.74) with thyroid-specific associations in trans with TMEM253 and ARFGEF3 (P ≤ 2.2 × 10−16 for both with rs1867277; Fig. 6a and Extended Data Fig. 16). The 9q22 locus has previously been linked to multiple thyroid-specific diseases including goitre, hypothyroidism and thyroid cancer48,49, and loss-of- function mutations in a thyroid-specific transcription factor at this locus, FOXE1, manifest as ectopic thyroid tissue or cleft palate in developing mice. However, the mechanism of any cis-effects of these trans-eVariants remains uncertain from the GTEx data; a post hoc analysis demonstrated that PEER correction removed broad regulatory signals from the 9q22 locus, and particularly from cis- and trans-eQTL signals for FOXE1 (Supplementary Information 17). In PEER-corrected data, cis- and trans-eQTL signals co-localized for another cis-eGene in 9q22, TRMO, for both trans-eGenes43 (posterior probability >0.99). Mendelian randomization analysis of the PEER-corrected data supported the idea that TRMO regulates TMEM253 (P ≤1.3×10−9) and ARFGEF3 (P ≤2.1×10−11) based on trans-eVariant rs1867277. By contrast, FOXE1 had weak
