Most previous efforts to look at tissue dependency of cis-eQTL effects have only used a P-value threshold but this has obvious limitations. Here, we employed several complementary approaches in addition to the threshold-based approach to address this question. First, we assessed tissue dependency by studying shared effects at 1% FDR and found substantial tissue independency of cis-eQTLs (Table 1). For instance, 47% of cis-eQTLs identified at 1% FDR in adipose tissue are shared in at least one other tissue and as many as 22% are seen across all three tissues at a similar FDR threshold. This degree of sharing was further confirmed by estimating the proportion of significant results across tissues (π1=0.5-0.7) (Supplementary Fig. 4). As with previous smaller studies 9-11,13, tissue independent cis-eQTLs had larger effect sizes and were over-represented close to transcription start sites compared to tissue dependent effects (Supplementary Fig. 5). In general, cis-effects located less than 200kb from TSS explain a larger proportion of the variance in expression levels (r2average_adipose=0.07, r2average_LCL=0.08, r2average_skin=0.08) than long-range effects (located >200 kb from TSS) (r2average_adipose=0.04, r2average_LCL=0.04, r2average_skin=0.04) (Supplementary Fig. 6).
