Epistasis: obstacle or advantage for mapping complex traits?
Identification of genetic loci in complex traits has focused largely on one-dimensional genome scans to search for associations between single markers and the phenotype. There is mounting evidence that locus interactions, or epistasis, are a crucial component of the genetic architecture of biologica...
| Main Authors: | , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2010-08-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC2928725?pdf=render |
| _version_ | 1811276897621901312 |
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| author | Koen J F Verhoeven George Casella Lauren M McIntyre |
| author_facet | Koen J F Verhoeven George Casella Lauren M McIntyre |
| author_sort | Koen J F Verhoeven |
| collection | DOAJ |
| description | Identification of genetic loci in complex traits has focused largely on one-dimensional genome scans to search for associations between single markers and the phenotype. There is mounting evidence that locus interactions, or epistasis, are a crucial component of the genetic architecture of biologically relevant traits. However, epistasis is often viewed as a nuisance factor that reduces power for locus detection. Counter to expectations, recent work shows that fitting full models, instead of testing marker main effect and interaction components separately, in exhaustive multi-locus genome scans can have higher power to detect loci when epistasis is present than single-locus scans, and improvement that comes despite a much larger multiple testing alpha-adjustment in such searches. We demonstrate, both theoretically and via simulation, that the expected power to detect loci when fitting full models is often larger when these loci act epistatically than when they act additively. Additionally, we show that the power for single locus detection may be improved in cases of epistasis compared to the additive model. Our exploration of a two step model selection procedure shows that identifying the true model is difficult. However, this difficulty is certainly not exacerbated by the presence of epistasis, on the contrary, in some cases the presence of epistasis can aid in model selection. The impact of allele frequencies on both power and model selection is dramatic. |
| first_indexed | 2024-04-13T00:06:03Z |
| format | Article |
| id | doaj.art-9f05ee25a8e640dfa8f4c748e46c8e2e |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-04-13T00:06:03Z |
| publishDate | 2010-08-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-9f05ee25a8e640dfa8f4c748e46c8e2e2022-12-22T03:11:14ZengPublic Library of Science (PLoS)PLoS ONE1932-62032010-08-0158e1226410.1371/journal.pone.0012264Epistasis: obstacle or advantage for mapping complex traits?Koen J F VerhoevenGeorge CasellaLauren M McIntyreIdentification of genetic loci in complex traits has focused largely on one-dimensional genome scans to search for associations between single markers and the phenotype. There is mounting evidence that locus interactions, or epistasis, are a crucial component of the genetic architecture of biologically relevant traits. However, epistasis is often viewed as a nuisance factor that reduces power for locus detection. Counter to expectations, recent work shows that fitting full models, instead of testing marker main effect and interaction components separately, in exhaustive multi-locus genome scans can have higher power to detect loci when epistasis is present than single-locus scans, and improvement that comes despite a much larger multiple testing alpha-adjustment in such searches. We demonstrate, both theoretically and via simulation, that the expected power to detect loci when fitting full models is often larger when these loci act epistatically than when they act additively. Additionally, we show that the power for single locus detection may be improved in cases of epistasis compared to the additive model. Our exploration of a two step model selection procedure shows that identifying the true model is difficult. However, this difficulty is certainly not exacerbated by the presence of epistasis, on the contrary, in some cases the presence of epistasis can aid in model selection. The impact of allele frequencies on both power and model selection is dramatic.http://europepmc.org/articles/PMC2928725?pdf=render |
| spellingShingle | Koen J F Verhoeven George Casella Lauren M McIntyre Epistasis: obstacle or advantage for mapping complex traits? PLoS ONE |
| title | Epistasis: obstacle or advantage for mapping complex traits? |
| title_full | Epistasis: obstacle or advantage for mapping complex traits? |
| title_fullStr | Epistasis: obstacle or advantage for mapping complex traits? |
| title_full_unstemmed | Epistasis: obstacle or advantage for mapping complex traits? |
| title_short | Epistasis: obstacle or advantage for mapping complex traits? |
| title_sort | epistasis obstacle or advantage for mapping complex traits |
| url | http://europepmc.org/articles/PMC2928725?pdf=render |
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