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Chunk #22 — Discussion

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How to deal with the early GWAS data when imputing and combining different arrays is necessary.
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The results presented here, were based on an early scan data with a small sample size. When combining modern arrays within studies, less bias may be expected due to better genotyping quality. On the other hand, the enormous sample size of pooled studies may amplify even the small individual effects, for example, due to platform effects, population strata, or genotyping batch effects, resulting in false positive findings, as heterogeneity between studies is amplified by imputation. Imputation of genotypes while combining different data sets can be a very powerful method, and has identified susceptibility loci using early scan data.17, 18 However, our findings stress that when combining newer data sets with early scan data rigorous QCs should be applied to ensure reproducible findings including pre- and postanalysis stages. Moreover, we recommend that post-analysis QC measures should be reported in publications as they give the most direct insight into influence of imputation on association.