Maintenance of Complex Trait Variation: Classic Theory and Modern Data

Numerous studies have found evidence that GWAS loci experience negative selection, which increases in intensity with the effect size of identified variants. However, there is also accumulating evidence that this selection is not entirely mediated by the focal trait and contains a substantial pleiotr...

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Autores principales:	Evan M. Koch, Shamil R. Sunyaev
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	population genetics genome-wide association study statistical genetics evolution quantitative genetics Genetics QH426-470
Acceso en línea:	https://doaj.org/article/3c50ac8de3484bfab77b15b9934cc6ab
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spelling	oai:doaj.org-article:3c50ac8de3484bfab77b15b9934cc6ab2021-11-12T12:28:46ZMaintenance of Complex Trait Variation: Classic Theory and Modern Data1664-802110.3389/fgene.2021.763363https://doaj.org/article/3c50ac8de3484bfab77b15b9934cc6ab2021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fgene.2021.763363/fullhttps://doaj.org/toc/1664-8021Numerous studies have found evidence that GWAS loci experience negative selection, which increases in intensity with the effect size of identified variants. However, there is also accumulating evidence that this selection is not entirely mediated by the focal trait and contains a substantial pleiotropic component. Understanding how selective constraint shapes phenotypic variation requires advancing models capable of balancing these and other components of selection, as well as empirical analyses capable of inferring this balance and how it is generated by the underlying biology. We first review the classic theory connecting phenotypic selection to selection at individual loci as well as approaches and findings from recent analyses of negative selection in GWAS data. We then discuss geometric theories of pleiotropic selection with the potential to guide future modeling efforts. Recent findings revealing the nature of pleiotropic genetic variation provide clues to which genetic relationships are important and should be incorporated into analyses of selection, while findings that effect sizes vary between populations indicate that GWAS measurements could be misleading if effect sizes have also changed throughout human history.Evan M. KochEvan M. KochShamil R. SunyaevShamil R. SunyaevFrontiers Media S.A.articlepopulation geneticsgenome-wide association studystatistical geneticsevolutionquantitative geneticsGeneticsQH426-470ENFrontiers in Genetics, Vol 12 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	population genetics genome-wide association study statistical genetics evolution quantitative genetics Genetics QH426-470
spellingShingle	population genetics genome-wide association study statistical genetics evolution quantitative genetics Genetics QH426-470 Evan M. Koch Evan M. Koch Shamil R. Sunyaev Shamil R. Sunyaev Maintenance of Complex Trait Variation: Classic Theory and Modern Data
description	Numerous studies have found evidence that GWAS loci experience negative selection, which increases in intensity with the effect size of identified variants. However, there is also accumulating evidence that this selection is not entirely mediated by the focal trait and contains a substantial pleiotropic component. Understanding how selective constraint shapes phenotypic variation requires advancing models capable of balancing these and other components of selection, as well as empirical analyses capable of inferring this balance and how it is generated by the underlying biology. We first review the classic theory connecting phenotypic selection to selection at individual loci as well as approaches and findings from recent analyses of negative selection in GWAS data. We then discuss geometric theories of pleiotropic selection with the potential to guide future modeling efforts. Recent findings revealing the nature of pleiotropic genetic variation provide clues to which genetic relationships are important and should be incorporated into analyses of selection, while findings that effect sizes vary between populations indicate that GWAS measurements could be misleading if effect sizes have also changed throughout human history.
format	article
author	Evan M. Koch Evan M. Koch Shamil R. Sunyaev Shamil R. Sunyaev
author_facet	Evan M. Koch Evan M. Koch Shamil R. Sunyaev Shamil R. Sunyaev
author_sort	Evan M. Koch
title	Maintenance of Complex Trait Variation: Classic Theory and Modern Data
title_short	Maintenance of Complex Trait Variation: Classic Theory and Modern Data
title_full	Maintenance of Complex Trait Variation: Classic Theory and Modern Data
title_fullStr	Maintenance of Complex Trait Variation: Classic Theory and Modern Data
title_full_unstemmed	Maintenance of Complex Trait Variation: Classic Theory and Modern Data
title_sort	maintenance of complex trait variation: classic theory and modern data
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/3c50ac8de3484bfab77b15b9934cc6ab
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Maintenance of Complex Trait Variation: Classic Theory and Modern Data

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