作者: Edwin Choy , Roman Yelensky , Sasha Bonakdar , Robert M. Plenge , Richa Saxena
DOI: 10.1371/JOURNAL.PGEN.1000287
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摘要: Lymphoblastoid cell lines (LCLs), originally collected as renewable sources of DNA, are now being used a model system to study genotype–phenotype relationships in human cells, including searches for QTLs influencing levels individual mRNAs and responses drugs radiation. In the course attempting map genes drug response using 269 LCLs from International HapMap Project, we evaluated extent which biological noise non-genetic confounders contribute trait variability LCLs. While could be technically well measured on given day, observed significant day-to-day substantial correlation confounders, such baseline growth rates metabolic state culture. After correcting these were unable detect any with genome-wide significance response. A much higher proportion variance mRNA may attributed factors (intra-individual variance—i.e., noise, EBV virus transform ATP levels) than detectable eQTLs. Finally, an attempt improve power, focused analysis those that had both eQTLs response; evidence eQTL SNPs convincingly associated model. promising pharmacogenetic experiments, vitro artifacts reduce power have potential create spurious association due confounding.