An evolutionary perspective on epistasis and the missing heritability.

The relative importance between additive and non-additive genetic variance has been widely argued in quantitative genetics. By approaching this question from an evolutionary perspective we show that, while additive variance can be maintained under selection at a low level for some patterns of epista...

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Autores principales:	Gibran Hemani, Sara Knott, Chris Haley
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2013
Materias:	Genetics QH426-470
Acceso en línea:	https://doaj.org/article/495d52cd492c4acea5b47aa6e3912327
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spelling	oai:doaj.org-article:495d52cd492c4acea5b47aa6e39123272021-11-18T06:19:59ZAn evolutionary perspective on epistasis and the missing heritability.1553-73901553-740410.1371/journal.pgen.1003295https://doaj.org/article/495d52cd492c4acea5b47aa6e39123272013-02-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23509438/pdf/?tool=EBIhttps://doaj.org/toc/1553-7390https://doaj.org/toc/1553-7404The relative importance between additive and non-additive genetic variance has been widely argued in quantitative genetics. By approaching this question from an evolutionary perspective we show that, while additive variance can be maintained under selection at a low level for some patterns of epistasis, the majority of the genetic variance that will persist is actually non-additive. We propose that one reason that the problem of the "missing heritability" arises is because the additive genetic variation that is estimated to be contributing to the variance of a trait will most likely be an artefact of the non-additive variance that can be maintained over evolutionary time. In addition, it can be shown that even a small reduction in linkage disequilibrium between causal variants and observed SNPs rapidly erodes estimates of epistatic variance, leading to an inflation in the perceived importance of additive effects. We demonstrate that the perception of independent additive effects comprising the majority of the genetic architecture of complex traits is biased upwards and that the search for causal variants in complex traits under selection is potentially underpowered by parameterising for additive effects alone. Given dense SNP panels the detection of causal variants through genome-wide association studies may be improved by searching for epistatic effects explicitly.Gibran HemaniSara KnottChris HaleyPublic Library of Science (PLoS)articleGeneticsQH426-470ENPLoS Genetics, Vol 9, Iss 2, p e1003295 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Genetics QH426-470
spellingShingle	Genetics QH426-470 Gibran Hemani Sara Knott Chris Haley An evolutionary perspective on epistasis and the missing heritability.
description	The relative importance between additive and non-additive genetic variance has been widely argued in quantitative genetics. By approaching this question from an evolutionary perspective we show that, while additive variance can be maintained under selection at a low level for some patterns of epistasis, the majority of the genetic variance that will persist is actually non-additive. We propose that one reason that the problem of the "missing heritability" arises is because the additive genetic variation that is estimated to be contributing to the variance of a trait will most likely be an artefact of the non-additive variance that can be maintained over evolutionary time. In addition, it can be shown that even a small reduction in linkage disequilibrium between causal variants and observed SNPs rapidly erodes estimates of epistatic variance, leading to an inflation in the perceived importance of additive effects. We demonstrate that the perception of independent additive effects comprising the majority of the genetic architecture of complex traits is biased upwards and that the search for causal variants in complex traits under selection is potentially underpowered by parameterising for additive effects alone. Given dense SNP panels the detection of causal variants through genome-wide association studies may be improved by searching for epistatic effects explicitly.
format	article
author	Gibran Hemani Sara Knott Chris Haley
author_facet	Gibran Hemani Sara Knott Chris Haley
author_sort	Gibran Hemani
title	An evolutionary perspective on epistasis and the missing heritability.
title_short	An evolutionary perspective on epistasis and the missing heritability.
title_full	An evolutionary perspective on epistasis and the missing heritability.
title_fullStr	An evolutionary perspective on epistasis and the missing heritability.
title_full_unstemmed	An evolutionary perspective on epistasis and the missing heritability.
title_sort	evolutionary perspective on epistasis and the missing heritability.
publisher	Public Library of Science (PLoS)
publishDate	2013
url	https://doaj.org/article/495d52cd492c4acea5b47aa6e3912327
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An evolutionary perspective on epistasis and the missing heritability.

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