As shown in Table S3, the SNPs modulating transcript levels had small effect sizes in our joint GWAS association results, the highest odds ratio (OR) being 1.13. We used PS v3.0 [38] for statistical power calculations to determine the required sample size for a third genotypic replication of such SNPs. In order to replicate an association for one SNP with minor allele frequency 0.35 at α = 0.05, one would require a minimum of 2,250 cases and 2,250 controls to achieve 80% power for detecting an effect with OR 1.13. As shown in Table 1, several eQTL SNPs did not reach Bonferroni corrected significance in the replication data alone, but do show stronger effects in the joint GWAS data, indicating that statistical power of the GWAS replication set might be a limiting factor. By testing these SNPs in a third independent replication cohort, additional true associations may be detected. The required sample size for such an effort would, however, increase dramatically when adding more tests. Further international collaboration, therefore, is needed in order to achieve sufficient statistical power for the replication of SNPs with small effect sizes.
