Accurate and equitable medical genomic analysis requires an understanding of demography and its influence on sample size and ratio.


: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:


Genome Biol


Genome biology


Kessler MD,O'Connor TD




Has Abstract


2017-02-27 00:00:00














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    pub_type: 杂志文章


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    更新日期:2003-01-01 00:00:00

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    authors: Kentepozidou E,Aitken SJ,Feig C,Stefflova K,Ibarra-Soria X,Odom DT,Roller M,Flicek P

    更新日期:2020-01-07 00:00:00

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    authors: Lin C,Todo T

    更新日期:2005-01-01 00:00:00

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    更新日期:2020-04-28 00:00:00

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    authors: McGregor K,Bernatsky S,Colmegna I,Hudson M,Pastinen T,Labbe A,Greenwood CM

    更新日期:2016-05-03 00:00:00

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    authors: Kilpinen S,Autio R,Ojala K,Iljin K,Bucher E,Sara H,Pisto T,Saarela M,Skotheim RI,Björkman M,Mpindi JP,Haapa-Paananen S,Vainio P,Edgren H,Wolf M,Astola J,Nees M,Hautaniemi S,Kallioniemi O

    更新日期:2008-01-01 00:00:00

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