In order to annotate variants by their effect on regulatory motifs, a library of position weight matrices (PWMs) was constructed from literature sources and was scored on genomic sequences as described previously (6). Briefly, a set of PWMs was collected from TRANSFAC (25), JASPAR (26), and protein-binding microarray (PBM) experiments (27–29). The reference and alternate alleles for each of the 1000 Genomes pilot SNPs and indels were concatenated with 29 bp of genomic context on each side, using the hg18 sequence obtained from the UCSC Genome Browser (30). PWMs were then scored for instances that passed either of two thresholds, a stringent threshold of P < 4−8 and a less-stringent threshold of P < 4−7 (31). Only instances where a motif in the sequence (i) passed the stringent threshold of a PWM in either the reference or the alternate genomic sequence, and (ii) overlapped the variable nucleotide(s) (thus changing the PWM score) were considered. Then, the change in log-odds (LOD) score was calculated. In cases where the weaker match was did not pass the less-stringent threshold, an approximate minimum change
