title: Accurate and equitable medical genomic analysis requires an understanding of demography and its influence on sample size and ratio.
abstract: In a recent study, Petrovski and Goldstein reported that (non-Finnish) Europeans have significantly fewer nonsynonymous singletons in Online Mendelian Inheritance in Man (OMIM) disease genes compared with Africans, Latinos, South Asians, East Asians, and other unassigned non-Europeans. We use simulations of Exome Aggregation Consortium (ExAC) data to show that sample size and ratio interact to influence the number of these singletons identified in a cohort. These interactions are different across ancestries and can lead to the same number of identified singletons in both Europeans and non-Europeans without an equal number of samples. We conclude that there is a need to account for the ancestry-specific influence of demography on genomic architecture and rare variant analysis in order to address inequalities in medical genomic analysis.The authors of the original article were invited to submit a response, but declined to do so. Please see related Open Letter: http://genomebiology.biomedcentral.com/articles/10.1186/s13059-016-1016-y.
authors.affiliation: Institute for Genome Sciences, University of Maryland School of Medicine, Baltimore, MD, 21201, USA. Michael.Kessler@som.umaryland.edu.|Department of Medicine, University of Maryland School of Medicine, Baltimore, MD, 21201, USA. Michael.Kessler@som.umaryland.edu.|Program in Personalized and Genomic Medicine, University of Maryland School of Medicine, Baltimore, MD, 21201, USA. Michael.Kessler@som.umaryland.edu.
authors.forename: Michael D
authors.identifier: 0000-0003-1258-5221
authors.initials: MD
authors.lastname: Kessler
authors.affiliation: Institute for Genome Sciences, University of Maryland School of Medicine, Baltimore, MD, 21201, USA. TOConnor@som.umaryland.edu.|Department of Medicine, University of Maryland School of Medicine, Baltimore, MD, 21201, USA. TOConnor@som.umaryland.edu.|Program in Personalized and Genomic Medicine, University of Maryland School of Medicine, Baltimore, MD, 21201, USA. TOConnor@som.umaryland.edu.|University of Maryland Marlene and Stewart Greenebaum Comprehensive Cancer Center, Baltimore, MD, 21201, USA. TOConnor@som.umaryland.edu.
authors.forename: Timothy D
authors.initials: TD
authors.lastname: O'Connor
mesh_terms: D003710:Demography; D005006:Ethnicity; D023281:Genomics / Q000379:methods* / Q000592:standards*; D006801:Humans; D015203:Reproducibility of Results; D018401:Sample Size