Meta-analysis was performed by extending the analysis of the different array sets run on the pools. First the difference between case and control allele frequencies was computed for each SNP in the Dutch data set. The results for each SNP were then combined by calculating a composite version of T_2_X which weighted the pooling (Australian data) and individual genotyping (Dutch data) frequency difference values by the inverse of their variance. For the pool data, the variance comprised the binomial sampling variance, together with the terms vare_pool_2 and varSNPspecific. For the individual genotyping data, the variance comprised just the binomial sampling variance. In a limited number of cases, the allele frequency estimates from pooling were different from those obtained from individual genotyping; this was due largely to the potential for unequal amplification of alleles in the pooling analysis. To minimize the effects of this on the meta-analysis results, SNPs with minor allele frequency less than 5% (as measured in the Dutch samples) were filtered out in the final analysis. Our study had very limited power to detect variants with small minor allele frequencies so this is unlikely to have adversely affected results.
