Schröder, Adrian and Klein, Kathrin and Winter, Stefan and Schwab, Matthias and Bonin, Michael and Zell, Andreas and Zanger, Ulrich M.

Genomics of ADME gene expression: mapping expression quantitative trait loci relevant for absorption, distribution, metabolism and excretion of drugs in human liver

The Pharmacogenomics Journal (2011), pp. 1473-1150


Abstract

Expression quantitative trait loci (eQTL) analysis is a powerful approach toward identifying genetic loci associated with quantitative changes in gene expression. We applied genome-wide association analysis to a data set of 4300 000 single-nucleotide polymorphisms and 48 000 mRNA expression phenotypes obtained by Illumina microarray profiling of 149 human surgical liver samples obtained from Caucasian donors with detailed medical documentation. Of 1 226 significant associations, only 200 were validated when comparing with a previously published similar study. Potential explanations for low replication rate include differences in microarray platforms, statistical modeling, covariates considered and origin and collection procedures of tissues. Focused analysis revealed a subset of 95 associations related to absorption, distribution, metabolism and excretion of drugs. Of these, 21 were true replications and 74 were newly discovered associations in enzymes, transporters, transcriptional regulators and other genes. This study extends our knowledge about the genetics of interindividual variability of gene expression with particular emphasis on pharmacogenomics.


Downloads and Links

[doi] [pdf] [pdf]


BibTeX

@article{Schroeder2011c,
  author = {Schr\"oder, Adrian and Klein, Kathrin and Winter, Stefan and Schwab,
	Matthias and Bonin, Michael and Zell, Andreas and Zanger, Ulrich
	M.},
  title = {{Genomics of ADME gene expression: mapping expression quantitative
	trait loci relevant for absorption, distribution, metabolism and
	excretion of drugs in human liver}},
  journal = {The Pharmacogenomics Journal},
  year = {2011},
  pages = {1473--1150},
  month = sep,
  abstract = {Expression quantitative trait loci (eQTL) analysis is a powerful approach
	toward identifying genetic loci associated with quantitative changes
	in gene expression. We applied genome-wide association analysis to
	a data set of 4300\,000 single-nucleotide polymorphisms and 48 000
	mRNA expression phenotypes obtained by Illumina microarray profiling
	of 149 human surgical liver samples obtained from Caucasian donors
	with detailed medical documentation. Of 1\,226 significant associations,
	only 200 were validated when comparing with a previously published
	similar study. Potential explanations for low replication rate include
	differences in microarray platforms, statistical modeling, covariates
	considered and origin and collection procedures of tissues. Focused
	analysis revealed a subset of 95 associations related to absorption,
	distribution, metabolism and excretion of drugs. Of these, 21 were
	true replications and 74 were newly discovered associations in enzymes,
	transporters, transcriptional regulators and other genes. This study
	extends our knowledge about the genetics of interindividual variability
	of gene expression with particular emphasis on pharmacogenomics.},
  doi = {10.1038/tpj.2011.44},
  keywords = {ADME, eQTL, gene expression, pharmacogenetics, quantitative trait
	loci, SNP},
  pdf = {http://www.nature.com/tpj/journal/vaop/ncurrent/pdf/tpj201144a.pdf},
  url = {http://dx.doi.org/10.1038/tpj.2011.44}
}