The genetic architecture of gene expression in individuals of African and European ancestry
Fletez-Brant, K.; Sauteraud, R.; Liang, Y.; Micheletti, S.; Nandakumar, P.; Sugathan, A.; Song, K.; Cavazos, T. B.; Thomas, A.; Tunney, R. J.; Hicks, B.; O'Connell, J.; Shringarpure, S. S.; Kukar, K.; Moreno, M.; DelloRusso, E.; Wong, C. D.; Petrakovitz, A.; Atla, G.; Cortes, A.; Gormley, P.; Howe, L.; Mishra, R.; Seaton, D.; the 23andMe Research Team, ; Gentleman, R. C.; Pitts, S. J.; Vacic, V.
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We conducted two large scale studies of the genetics of gene expression in individuals of African ancestry within a cohort of consented 23andMe research participants and in LCL samples from the 1000 Genomes Project African superpopulation. We discovered nearly four times as many eQTLs, compared to tissue-matched eQTL studies in European cohorts. Additionally, we found that the majority of eQTLs were not detectable across populations; those that were, however, were found to be highly concordant. Performing eQTL studies in African ancestry cohorts resulted in more signals per gene and smaller credible sets of causal variants. We showed that comparisons of heritability of gene expression could be confounded by population substructure, but that variation in local genetic ancestry did not majorly impact eQTL discovery. Finally, we showed improvements in variant-to-gene mapping of African-American GWAS signals when using African compared to European ancestry eQTL studies
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