Figure 1 shows the Manhattan plot of the primary results. Four independent regions contained SNPs with p<5×10−8 (table 1; appendix pp 34–35, 25–33). The strongest association signal was on chromosome 3 at an intronic SNP within ITIH3 (table 1). This SNP is in linkage disequilibrium with SNPs encompassing several genes across a 1 Mb region (appendix p 22). The second strongest signal was in an intron of AS3MT on chromosome 10q24 (table 1). Linkage disequilibrium around this associated region encompasses several genes including CNNM2. We also recorded genome-wide significant association within CACNA1C, and finally detected significant association to a second locus on chromosome 10 in an intron of CACNB2 (table 1). We undertook conditional analyses to assess evidence for multirisk loci in a region. In these analyses, we included the most strongly associated or peak SNP plus any SNPs within 1·5 Mb of the peak SNP with association p values less than 10−4 and r2 less than 0·2 with the peak SNP based on HapMap 3 CEU data. For the chromosome 3p21 region, and regions CACNA1C and CACNB2, no additional
