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

Autor: Deflaux N; Verily Life Sciences, San Francisco, CA, USA., Selvaraj MS; Program in Medical and Population Genetics and the Cardiovascular Disease Initiative, Broad Institute of Harvard and MIT, Cambridge, MA, USA.; Department of Medicine, Harvard Medical School, Boston, MA, USA.; Cardiovascular Research Center, Massachusetts General Hospital, Boston, MA, USA.; Center for Genomic Medicine, Massachusetts General Hospital, Boston, MA, USA., Condon HR; Division of Genetic Medicine, Vanderbilt University Medical Center, Nashville, TN, USA., Mayo K; Vanderbilt Institute for Clinical and Translational Research, Vanderbilt University Medical Center, Nashville, TN, USA., Haidermota S; Program in Medical and Population Genetics and the Cardiovascular Disease Initiative, Broad Institute of Harvard and MIT, Cambridge, MA, USA.; Division of Cardiology, Massachusetts General Hospital, Boston, MA, USA., Basford MA; Vanderbilt Institute for Clinical and Translational Research, Vanderbilt University Medical Center, Nashville, TN, USA., Lunt C; All of Us Research Program, National Institutes of Health, Bethesda, MD, USA., Philippakis AA; Broad Institute of Harvard and MIT, Cambridge, MA, USA., Roden DM; Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA.; Department of Pharmacology, Vanderbilt University Medical Center, Nashville, TN, USA.; Department of Biomedical Informatics, Vanderbilt University Medical Center, Nashville, TN, USA., Denny JC; All of Us Research Program, National Institutes of Health, Bethesda, MD, USA., Musick A; All of Us Research Program, National Institutes of Health, Bethesda, MD, USA., Collins R; Nuffield Department of Population Health, University of Oxford, Oxford, Oxfordshire, UK.; UK Biobank, Cheadle, Stockport, UK., Allen N; Nuffield Department of Population Health, University of Oxford, Oxford, Oxfordshire, UK.; UK Biobank, Cheadle, Stockport, UK., Effingham M; UK Biobank, Cheadle, Stockport, UK., Glazer D; Verily Life Sciences, San Francisco, CA, USA., Natarajan P; Program in Medical and Population Genetics and the Cardiovascular Disease Initiative, Broad Institute of Harvard and MIT, Cambridge, MA, USA.; Department of Medicine, Harvard Medical School, Boston, MA, USA.; Cardiovascular Research Center, Massachusetts General Hospital, Boston, MA, USA.; Center for Genomic Medicine, Massachusetts General Hospital, Boston, MA, USA.; Division of Cardiology, Massachusetts General Hospital, Boston, MA, USA., Bick AG; Division of Genetic Medicine, Vanderbilt University Medical Center, Nashville, TN, USA. alexander.bick@vumc.org.
Jazyk: angličtina
Zdroj: Nature communications [Nat Commun] 2023 Sep 05; Vol. 14 (1), pp. 5419. Date of Electronic Publication: 2023 Sep 05.
DOI: 10.1038/s41467-023-41185-x
Abstrakt: 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 2  ~ 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.
(© 2023. Springer Nature Limited.)
Databáze: MEDLINE
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