Statistical colocalisation analysis is limited to instances where full summary statistics are available for both traits. For other disease traits available in the GWAS catalogue, we searched for sharing of lead iPSC-specific eQTL and GWAS SNPs. We found six variants where the lead eQTL variant was identical to a catalogued GWAS variant, with no other common variants in LD (r2 < 0.8). One example was rs10069690, the lead eQTL variant for the TERT (Telomerase Reverse Transcriptase) gene (Fig. 5b). Although this variant is associated with germline predisposition to seven cancers33–35, this eQTL is not reported in cancer eQTL studies36–38 nor in any GTEx tissue. Previous studies have reported aberrant splicing of TERT caused by rs1006969039. We quantified TERT intron retention rates and found that the minor allele of rs10069690 increased the fraction of TERT transcripts in which intron four is retained (P = 1.7x10-9, Bonferroni adjusted) (Fig. 5d, Extended Data Fig. 10). Somatic TERT promoter mutations only manifest in differentiated cells, resulting in increased telomerase activity40. We speculate that the germline TERT eQTL we identified in iPSCs results in genotype-dependent variability in telomerase activity in somatic cell types, leading to differential cancer susceptibility.
