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.

journal_name

Genome Biol

journal_title

Genome biology

authors

Kessler MD,O'Connor TD

doi

10.1186/s13059-017-1172-8

subject

Has Abstract

pub_date

2017-02-27 00:00:00

pages

42

issue

1

eissn

1474-7596

issn

1474-760X

pii

10.1186/s13059-017-1172-8

journal_volume

18

pub_type

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