Demonstrating paths for unlocking the value of cloud genomics through cross cohort analysis.

Deflaux, Nicole; Selvaraj, Margaret Sunitha; Condon, Henry Robert; Mayo, Kelsey; Haidermota, Sara; Basford, Melissa A; Lunt, Chris; Philippakis, Anthony A et al. · Nat Commun · 2023

meta_analysis · Level I

Where this comes from

Abstract

Recently, large scale genomic projects such as All of Us and the UK Biobank have introduced a new research paradigm where data are stored centrally in cloud-based Trusted Research Environments (TREs). To characterize the advantages and drawbacks of different TRE attributes in facilitating cross-cohort analysis, we conduct a Genome-Wide Association Study of standard lipid measures using two approaches: meta-analysis and pooled analysis. Comparison of full summary data from both approaches with an external study shows strong correlation of known loci with lipid levels (R<sup>2</sup> ~ 83-97%). Importantly, 90 variants meet the significance threshold only in the meta-analysis and 64 variants are significant only in pooled analysis, with approximately 20% of variants in each of those groups being most prevalent in non-European, non-Asian ancestry individuals. These findings have important implications, as technical and policy choices lead to cross-cohort analyses generating similar, but not identical results, particularly for non-European ancestral populations.

Medical subject headings