Genetic Analysis of Drug Response and Gene Expression in Lymphoblastoid Cell Lines
Author Information
Author(s): Choy Edwin, Yelensky Roman, Bonakdar Sasha, Plenge Robert M., Saxena Richa, De Jager Philip L., Shaw Stanley Y., Wolfish Cara S., Slavik Jacqueline M., Cotsapas Chris, Rivas Manuel, Dermitzakis Emmanouil T., Cahir-McFarland Ellen, Kieff Elliott, Hafler David, Daly Mark J., Altshuler David
Primary Institution: Broad Institute of MIT and Harvard
Hypothesis
What are the genetic factors influencing drug response and gene expression in lymphoblastoid cell lines?
Conclusion
The study found that non-genetic factors significantly influence drug response and gene expression variability in lymphoblastoid cell lines, overshadowing the effects of genetic variants.
Supporting Evidence
- Drug responses were technically well measured but showed significant day-to-day variability.
- Non-genetic factors like growth rates and metabolic states were found to correlate strongly with drug responses.
- Genome-wide association studies did not reveal any SNPs associated with drug response at genome-wide significance.
Takeaway
Scientists studied how genes affect how cells respond to drugs, but found that other factors, like how fast the cells grow, matter more than the genes.
Methodology
The study used lymphoblastoid cell lines to evaluate drug responses and gene expression, measuring various cellular phenotypes and performing genome-wide association studies.
Potential Biases
Non-genetic confounding factors could create spurious associations between genetic variants and drug response.
Limitations
The study's sample size was relatively small, which may limit the power to detect weak genetic effects.
Participant Demographics
The study involved 269 lymphoblastoid cell lines derived from individuals in the International HapMap Project.
Digital Object Identifier (DOI)
Want to read the original?
Access the complete publication on the publisher's website