TY - JOUR
T1 - Enrichment analyses identify shared associations for 25 quantitative traits in over 600,000 individuals from seven diverse ancestries
AU - Smith, Samuel Pattillo
AU - Shahamatdar, Sahar
AU - Cheng, Wei
AU - Zhang, Selena
AU - Paik, Joseph
AU - Graff, Misa
AU - Haiman, Christopher
AU - Matise, T. C.
AU - North, Kari E.
AU - Peters, Ulrike
AU - Kenny, Eimear
AU - Gignoux, Chris
AU - Wojcik, Genevieve
AU - Crawford, Lorin
AU - Ramachandran, Sohini
N1 - Publisher Copyright:
© 2022 The Author(s)
PY - 2022/5/5
Y1 - 2022/5/5
N2 - 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 because of various confounding challenges. Here, we demonstrate that enrichment analyses that 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.
AB - 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 because of various confounding challenges. Here, we demonstrate that enrichment analyses that 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.
KW - GWAS, multi-ancestry, enrichment analyses
UR - http://www.scopus.com/inward/record.url?scp=85129411168&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85129411168&partnerID=8YFLogxK
U2 - 10.1016/j.ajhg.2022.03.005
DO - 10.1016/j.ajhg.2022.03.005
M3 - Article
C2 - 35349783
AN - SCOPUS:85129411168
SN - 0002-9297
VL - 109
SP - 871
EP - 884
JO - American journal of human genetics
JF - American journal of human genetics
IS - 5
ER -