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G3 (Bethesda). 2018 Aug 30;8(9):3059-3068. doi: 10.1534/g3.118.200571.

GWAS with Heterogeneous Data: Estimating the Fraction of Phenotypic Variation Mediated by Gene Expression Data.

Author information

1
Gregor Mendel Institute, Austrian Academy of Sciences, Vienna B(VBC), Vienna, Austria.
2
Center for Medical Statistics, Informatics, and Intelligent Systems, Medical University Vienna, Vienna, Austria.
3
Gregor Mendel Institute, Austrian Academy of Sciences, Vienna B(VBC), Vienna, Austria magnus.nordborg@gmi.oeaw.ac.at.

Abstract

Intermediate phenotypes such as gene expression values can be used to elucidate the mechanisms by which genetic variation causes phenotypic variation, but jointly analyzing such heterogeneous data are far from trivial. Here we extend a so-called mediation model to handle the confounding effects of genetic background, and use it to analyze flowering time variation in Arabidopsis thaliana, focusing in particular on the central role played by the key regulator FLOWERING TIME LOCUS C (FLC). FLC polymorphism and FLC expression are both strongly correlated with flowering time variation, but the effect of the former is only partly mediated through the latter. Furthermore, the latter also reflects genetic background effects. We demonstrate that it is possible to partition these effects, shedding light on the complex regulatory network that underlies flowering time variation.

KEYWORDS:

FLC; correlation network; genetic architecture; mediation analysis, flowering time; natural variation

PMID:
30068524
PMCID:
PMC6118313
DOI:
10.1534/g3.118.200571
[Indexed for MEDLINE]
Free PMC Article

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