Finally, we replicated two tissue-specific trans-eQTLs highlighted in the TwinsUK Multiple Tissue Human Expression Resource (MuTHER) study38,39 (n = 845 donors in three tissues: subcutaneous adipose, LCLs and skin). First, in sun-exposed skin in GTEx, rs289750 was associated in cis with NLRC5 (association P ≤4.7 ×10 −16) and in trans with TAP1 (association P ≤9.0 ×10 −10, 4.3% FDR in the cis-eQTL restricted trans-eQTL discovery set), while the TwinsUK study found rs289749 (located 469 bp away from rs289750; R2 =0.918) associated in skin samples with NLRC5 in cis (association P ≤2.2 ×10 −16) (ref. 38) and TAP1 in trans (tensor association P ≤4.3 ×10 −7) (ref. 39). Second, the MuTHER study identified a master regulator in subcutaneous adipose, rs4731702, associated with the maternally expressed cis target gene KLF14, which encodes the transcription factor Kruppel-like factor38,40. cis-eQTL rs4731702 showed enriched association with genes that are relevant in metabolic phenotypes, such as cholesterol levels. In the GTEx data, rs4731702 is in strong linkage disequilibrium with two variants, rs13234269 and rs35722851 (R2 =0.98 and 0.99, respectively), that are cis-eQTLs for KLF14 in subcutaneous
