Chad Myers (University of Minnesota, Minneapolis, MN, USA) and Manuel Mattheisen (Brigham and Williams Hospital, Boston, MA, USA) demonstrated approaches that group genes prior to testing for significant variants.
As a generality from common diseases, genetic risk factors discovered by GWAS have been modest in their effects (odds ratios 1 1.2) requiring sample sizes of several thousand to have the statistical power required for unequivocal detection of significant variants.
We were unable to subclassify patients because our analysis only takes into account the most significant variant for each gene, and more significant markers may be needed to identify such subgroups.
10 RegulomeDB revealed no other functionality for highly significant variants.
The technologies of choice in many laboratories for hemoglobinopathy screening are IEF and HPLC, which can detect the full range of more than 700 hemoglobin variants, including those in the core panel, for which clinically significant variants are reported.
SNPs allele frequencies for genome-wide significant variants along with IGAP meta-analysis variants that were replicated in our GWAS; allele frequencies are compared to those of 1000G reference superpopulations (HISP = Caribbean Hispanics; EUR = European; AFR = African; AM-ADMX = American Admixed; EAS = East Asian).
The variant match rate was calculated as the ratio of variants from different analyses found within common windows to all significant variants for a pair of analyses.
Significant variants were for the most part candidates in cancer-related genes as is shown in Table 1.
The displayed results include P-values, the δ j/ δ̄ values for the significant rare variant and the number of total common variants and rare variants along with the coefficients of the significant common/rare variants (with standard error).
Proportion test was applied to asses for significant differences in functional variant proportions with respect to size and type of polymorphism.
