Fig. 2

Validation of allelic imbalance detected at GWAS loci and other predicted sites. a We detected significant allelic imbalance (binomial P < 0.01) in CREB1 ChIP-seq sequence reads at variants at five disease- and trait-associated loci. b At rs2382818, sequence reads that failed to align when only single alleles were considered (top) were correctly aligned in an allele-aware alignment (bottom). The increase in aligned reads allowed for the detection of a CREB1 peak (black box) and allelic imbalance at the variant for which more reads were aligned containing the T allele than the A allele were aligned. Total sequence signal is displayed and reads are shaded based which allele they contain. c We detected a significantly greater proportion of reads containing the C allele of rs713875 than the G allele. d EMSA using purified CREB1 and labeled probes containing each allele at nine sites of allelic imbalance to test for allelic differences in binding. Alleles colored blue are predicted to bind CREB1 more strongly than alleles colored red. Allelic differences in protein binding consistent with these predictions were observed for starred (*) variants. Only CREB1-bound probe is shown. Similar results were observed in a replicate experiment