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Supplementary Data 2 lists the 69 different transcription factors whose DNA binding affinity was predicted to be affected by the 251 selected HGMD regulatory SNPs/mutations from the 13 different disease states under study. To evaluate the statistical significance of candidate SNPs, we performed permutation analysis by randomly selecting HapMap SNPs (Gibbs et al., 2003) within promoter regions of human protein coding genes, and by randomizing the ranking of the transcription factors with respect to phenotypes (Section 2). In the third step (C), overall rankings, characterizing the transcription regulatory roles of candidate SNPs in phenotype/disease, are calculated based on the integration of ranks of SNPs in each transcription factor (step 1) and ranks of transcription factors to phenotype/disease (Step 2). Limitations of regSNPs include its reliance on existing knowledge (e.g. disease/phenotype-related genes, and binding models for transcription factors). Here, human transcription factors selected from the TRANSFAC database (Supplementary Data 1) were treated as candidate gene

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