We thought that this pattern could indicate the presence of allelic heterogeneity, which has also been suggested by a separate study focusing on 2 markers in the region (Schulze, Detera-Wadleigh, Akula, Gupta, Kassem, Steele, Pearl, Strohmaier, Breuer, Schwarz, et al., in press), and which might reflect multiple underlying rare variants. In the presence of allelic heterogeneity, we would expect that multiple haplotypes would show association with BD. Using the 10 SNP window result from the haplotype analysis in the EA population, which provide p-values for each haplotype in addition to the OMNIBUS p-values, we investigated the proportion of haplotypes within each window that had p-values less than 0.05 (Figure 2). In the ANK3 region, there were many 10-SNP windows that had a high proportion of low p-value haplotypes (up to 75%, genome-wide average = 4.7%), with 2-5 haplotypes often being implicated. In order to see if this was unexpected in the genome, we smoothed the proportion of significant haplotypes across the genome and looked for other regions that matched or exceeded the maximum smoothed value found in ANK3. We found
