By considering only independent genotyped SNPs that are assumed to fully tag the causal variants, we can ignore LD among genotyped variants and between the causal variant and the genotyped variants. Thereby, we can greatly reduce the theoretical and numerical complexity of the MetaGAP calculator. However, a genotyped tag SNP does not necessarily capture the full variation of the causal variant present in that independent segment. Nevertheless, the inputs for SNP heritability used in the MetaGAP calculator are within-study GREML estimates of heritability, based on the available SNPs. Therefore, if these genotyped SNPs are in imperfect LD with the causal variants, this will lead to a downward bias in the SNP-based heritability estimates [42]. Hence, the imperfect tagging of the causal variants is likely to be absorbed by a downward bias in the SNP-based heritability estimates.
