ArticlePLoS genetics2008
Genetic analysis of human traits in vitro: drug response and gene expression in lymphoblastoid cell lines.
Article in PLoS genetics, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 148 papers, 2 of them syntheses that pooled it.
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Who cites it
148 citing papers in PubMed, 2 syntheses or guidelines pooled it, 217 citations in OpenAlex.
- Integration of genomics and transcriptomics predicts diabetic retinopathy susceptibility genes.eLife · 2020Pooled it
- Impact of NUDT15 polymorphisms on thiopurines-induced myelotoxicity and thiopurines tolerance dose.Oncotarget · 2017Pooled it
- Dissecting the genetics of the human transcriptome identifies novel trait-related trans-eQTLs and corroborates the regulatory relevance of non-protein coding loci†.Human molecular genetics · 2015Trial
- Quantitative estimates of inter-individual variability for new approach methodologies-based systemic safety toolbox using a population-based human in vitro model.Toxicological sciences : an official journal of the Society of Toxicology · 2026Article
- Distinct Co-methylation Patterns in African and European Populations and Their Genetic Associations.Genomics, proteomics & bioinformatics · 2025Article
- Quartet RNA reference materials improve the quality of transcriptomic data through ratio-based profiling.Nature biotechnology · 2024Article
- Removing unwanted variation between samples in Hi-C experiments.Briefings in bioinformatics · 2024Article
- Star allele search: a pharmacogenetic annotation database and user-friendly search tool of publicly available 1000 Genomes Project biospecimens.BMC genomics · 2024Article
- MMCL-CDR: enhancing cancer drug response prediction with multi-omics and morphology images contrastive representation learning.Bioinformatics (Oxford, England) · 2023Article
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- A conserved expression signature predicts growth rate and reveals cell & lineage-specific differences.PLoS computational biology · 2021Article
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- Transcribed B lymphocyte genes and multiple sclerosis risk genes are underrepresented in Epstein-Barr Virus hypomethylated regions.Genes and immunity · 2020Article
- Individual Differences in the Response of Human β-Lymphoblastoid Cells to the Cytotoxic, Mutagenic, and DNA-Damaging Effects of a DNA Methylating Agent,Chemical research in toxicology · 2019Article
- Methods for evaluating variability in human health dose-response characterization.Human and ecological risk assessment : HERA · 2019Article
- Estimating Sample-Specific Regulatory Networks.iScience · 2019Article
- Extensive epigenetic and transcriptomic variability between genetically identical human B-lymphoblastoid cells with implications in pharmacogenomics research.Scientific reports · 2019Article
- Identifying Extrinsic versus Intrinsic Drivers of Variation in Cell Behavior in Human iPSC Lines from Healthy Donors.Cell reports · 2019Article
- Dopamine perturbation of gene co-expression networks reveals differential response in schizophrenia for translational machinery.Translational psychiatry · 2018Article
- Transcriptomic signatures of schizophrenia revealed by dopamine perturbation in an ex vivo model.Translational psychiatry · 2018Article
88 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
17 authors at 3 institutions in 2 countries.
Funding
Abstract
Lymphoblastoid cell lines (LCLs), originally collected as renewable sources of DNA, are now being used as a model system to study genotype-phenotype relationships in human cells, including searches for QTLs influencing levels of individual mRNAs and responses to drugs and radiation. In the course of attempting to map genes for drug response using 269 LCLs from the International HapMap Project, we evaluated the extent to which biological noise and non-genetic confounders contribute to trait variability in LCLs. While drug responses could be technically well measured on a given day, we observed significant day-to-day variability and substantial correlation to non-genetic confounders, such as baseline growth rates and metabolic state in culture. After correcting for these confounders, we were unable to detect any QTLs with genome-wide significance for drug response. A much higher proportion of variance in mRNA levels may be attributed to non-genetic factors (intra-individual variance--i.e., biological noise, levels of the EBV virus used to transform the cells, ATP levels) than to detectable eQTLs. Finally, in an attempt to improve power, we focused analysis on those genes that had both detectable eQTLs and correlation to drug response; we were unable to detect evidence that eQTL SNPs are convincingly associated with drug response in the model. While LCLs are a promising model for pharmacogenetic experiments, biological noise and in vitro artifacts may reduce power and have the potential to create spurious association due to confounding.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.