Assumptions and properties of limiting pathway models for analysis of epistasis in complex traits

Stringer, Sven, Derks, Eske M., Kahn, Rene S., Hill, William G. and Wray, Naomi R. (2013) Assumptions and properties of limiting pathway models for analysis of epistasis in complex traits. PLoS One, 8 7: e68913.1-e68913.9. doi:10.1371/journal.pone.0068913

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Author Stringer, Sven
Derks, Eske M.
Kahn, Rene S.
Hill, William G.
Wray, Naomi R.
Title Assumptions and properties of limiting pathway models for analysis of epistasis in complex traits
Journal name PLoS One   Check publisher's open access policy
ISSN 1932-6203
Publication date 2013-07
Sub-type Article (original research)
DOI 10.1371/journal.pone.0068913
Open Access Status DOI
Volume 8
Issue 7
Start page e68913.1
End page e68913.9
Total pages 9
Place of publication San Francisco, CA, United States
Publisher Public Library of Science
Collection year 2014
Language eng
Abstract For most complex traits, results from genome-wide association studies show that the proportion of the phenotypic variance attributable to the additive effects of individual SNPs, that is, the heritability explained by the SNPs, is substantially less than the estimate of heritability obtained by standard methods using correlations between relatives. This difference has been called the "missing heritability". One explanation is that heritability estimates from family (including twin) studies are biased upwards. Zuket al. revisited overestimation of narrow sense heritability from twin studies as a result of confounding with non-additive genetic variance. They propose a limiting pathway (LP) model that generates significant epistatic variation and its simple parametrization provides a convenient way to explore implications of epistasis. They conclude that over-estimation of narrow sense heritability from family data ('phantom heritability') may explain an important proportion of missing heritability. We show that for highly heritable quantitative traits large phantom heritability estimates from twin studies are possible only if a large contribution of common environment is assumed. The LP model is underpinned by strong assumptions that are unlikely to hold, including that all contributing pathways have the same mean and variance and are uncorrelated. Here, we relax the assumptions that underlie the LP model to be more biologically plausible. Together with theoretical, empirical, and pragmatic arguments we conclude that in outbred populations the contribution of additive genetic variance is likely to be much more important than the contribution of non-additive variance.
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ
Additional Notes Article number e68913

Document type: Journal Article
Sub-type: Article (original research)
Collections: Queensland Brain Institute Publications
Official 2014 Collection
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Citation counts: TR Web of Science Citation Count  Cited 6 times in Thomson Reuters Web of Science Article | Citations
Scopus Citation Count Cited 7 times in Scopus Article | Citations
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