In the present study, we sought to apply one such approach based upon gene-wide analysis which offers a number of possible advantages over single locus tests5. First, if there is more than independent source of an association signal within a gene, for example where there is more than one functional variant, combining these into a single statistic might offer enhanced power over single SNP analysis. This is the main rationale underpinning our use of the truncated product approach23. Second, where there are true differences in the associated SNPs between studies, as might occur as a result of allelic heterogeneity, LD heterogeneity, or where this occurs simply as a result of the sometimes unpredictable nature of LD7,8, consistency of associations across studies may be easier to achieve at the gene-wide than at the SNP level. While such association may not provide a firm basis for implicating specific susceptibility variants, the identification of replicated associations can be of value in identifying candidate genes for further intensive genetic investigation and also for generating hypotheses concerning aetiology and pathophysiology. Both of the methods we
