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Chunk #49 — Online methods — GERA meta-analysis with ICBP, and with UKB

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Genome-wide association analyses using electronic health records identify new loci influencing blood pressure variation.
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We additionally performed meta-analysis of the GERA and ICBP results for genome-wide discovery using a fixed-effects meta-analysis, using UKB for replication. We further performed a discovery meta-analysis of GERA, ICBP and UKB for maximal discovery size, but with no replication sample available. In this analysis we reviewed the locus plots, manually merging the ±0.5Mb windows when necessary. Specifically, after assessing SNPs in the GERA+ICB+UKB meta-analysis, we checked if the SNPs appeared independent in a meta-analysis of GERA and UKB, as both had individual level data. Most regions were either obviously correlated with high r2, or obviously not with r2<0.05; however, to formalize the conditional analysis and retain a SNP as independent, we required that the reduction in p-values from univariate to joint in the GERA+UKB meta-analysis be less than 10-fold, and additionally that translating an equivalent reduction in p-values to the GERA+ICBP+UKB meta-analysis still led to a genome-wide significant result (i.e., if we assumed that Pjoint,GERA+ICBP+UKB/Punivariate,GERA+ICBP +UKB=Pjoint,G ERA+UKB/Punivariate,GERA+UKB, the approximated Pjoint,GERA+ICBP+UKB would still need to be genome-wide significant). This may have been slightly conservative.