302V Poster Online - Virtual Posters
Tuesday June 07, 11:00 AM - 3:00 PM

Authors:
Samuel Pattillo Smith ^1,2; Sahar Shahamatdar ^1,2; Wei Cheng ^1,2; Selena Zhang ¹; Misa Graff ³; Christopher Haiman ⁴; T.C. Matise ⁵; Kari E. North ³; Ulrike Peters ⁶; Eimear Kenny ^7,8,9,10; Chris Gignoux ¹¹; Genevieve Wojcik ¹²; Lorin Crawford ^1,13,14; Sohini Ramachandran ^1,2

Affiliations:
1) Center for Computational Molecular Biology, Brown University, Providence, RI; 2) Department of Ecology and Evolution, Brown University, Providence, RI; 3) Department of Epidemiology, University of North Carolina - Chapel Hill, Chapel Hill, NC; 4) Department of Preventative Medicine, University of Southern California, Los Angeles CA; 5) Department of Genetics, Rutgers University, Piscataway NJ ; 6) Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle WA; 7) The Center for Genomic Health, Icahn School of Medicine at Mount Sinai, New York City NY; 8) The Charles Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York City NY ; 9) Department of Medicine, Icahn School of Medicine at Mount Sinai, New York City NY; 10) Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai,22New York City NY ; 11) Division of Biomedical Informatics and Personalized Medicine, University of Colorado, Denver CO; 12) Department of Epidemiology, Johns Hopkins University, Baltimore MD ; 13) Department of Biostatistics, Brown University, Providence RI ; 14) Microsoft Research New England, Cambridge MA

Keywords:
Complex traits

Since 2005, genome-wide association (GWA) datasets have been largely biased toward sampling European ancestry individuals, and recent studies have shown that GWA results estimated from self-identified European individuals are not transferable to non-European individuals due to various confounding challenges. Here, we demonstrate that enrichment analyses which aggregate SNP-level association statistics at multiple genomic scales—from genes to genomic regions and pathways—have been underutilized in the GWA era and can generate biologically interpretable hypotheses regarding the genetic basis of complex trait architecture. We illustrate examples of the robust associations generated by enrichment analyses while studying 25 continuous traits assayed in 566,786 individuals from seven diverse self-identified human ancestries in the UK Biobank and the Biobank Japan, as well as 44,348 admixed individuals from the PAGE consortium including cohorts of African-American, Hispanic and Latin American, Native Hawaiian, and American Indian/Alaska Native individuals. We identify 1,000 gene-level associations that are genome-wide significant in at least two ancestry cohorts across these 25 traits, as well as highly conserved pathway associations with triglyceride levels in European, East Asian, and Native Hawaiian cohorts