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Accurate discovery of expression quantitative trait loci under confounding from spurious and genuine regulatory hotspots.

ABSTRACT: In genomewide mapping of expression quantitative trait loci (eQTL), it is widely believed that thousands of genes are trans-regulated by a small number of genomic regions called "regulatory hotspots," resulting in "trans-regulatory bands" in an eQTL map. As several recent studies have demonstrated, technical confounding factors such as batch effects can complicate eQTL analysis by causing many spurious associations including spurious regulatory hotspots. Yet little is understood about how these technical confounding factors affect eQTL analyses and how to correct for these factors. Our analysis of data sets with biological replicates suggests that it is this intersample correlation structure inherent in expression data that leads to spurious associations between genetic loci and a large number of transcripts inducing spurious regulatory hotspots. We propose a statistical method that corrects for the spurious associations caused by complex intersample correlation of expression measurements in eQTL mapping. Applying our intersample correlation emended (ICE) eQTL mapping method to mouse, yeast, and human identifies many more cis associations while eliminating most of the spurious trans associations. The concordances of cis and trans associations have consistently increased between different replicates, tissues, and populations, demonstrating the higher accuracy of our method to identify real genetic effects.

SUBMITTER: Kang HM

PROVIDER: S-EPMC2600931 | biostudies-literature | 2008 Dec

REPOSITORIES: biostudies-literature

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Accurate discovery of expression quantitative trait loci under confounding from spurious and genuine regulatory hotspots.

Kang Hyun Min HM Ye Chun C Eskin Eleazar E

Genetics 20080914 4

In genomewide mapping of expression quantitative trait loci (eQTL), it is widely believed that thousands of genes are trans-regulated by a small number of genomic regions called "regulatory hotspots," resulting in "trans-regulatory bands" in an eQTL map. As several recent studies have demonstrated, technical confounding factors such as batch effects can complicate eQTL analysis by causing many spurious associations including spurious regulatory hotspots. Yet little is understood about how these ...[more]

PMID: 18791227

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Accurate discovery of expression quantitative trait loci under confounding from spurious and genuine regulatory hotspots.

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Accurate discovery of expression quantitative trait loci under confounding from spurious and genuine regulatory hotspots.

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