Workshop in Biostatistics

M112 Alway Building, Medical Center

(next to the Dean's courtyard)

DATE: May 4, 2017
TIME: 1:30 - 2:50 pm
TITLE: The role of genetic evidence in drug discovery and development

Matthew R. Nelson, PhD
Head, Genetics
GSK, King of Prussia, PA



Discovering and developing new drugs to treat growing medical needs is immensely challenging and expensive.  Attrition is a major challenge, with >90% of projects failing before clinical trials and >50% of the remainder failing in clinical development due to lack of efficacy. Therefore, selecting and validating the best targets is the key decision in developing medicines.  The effect of genetic variants on measures of intermediate traits and disease can provide important insights into the causal biology of health and disease that can help guide the choice of drug targets and therapeutic mechanisms.  We demonstrate the contribution that genetic evidence can have in improving target selection decisions, the potential impact on drug discovery, and illustrate it with several examples.  Such observations are shaping drug discovery strategies across the industry.  Access to large-scale, densely genotyped and well phenotyped resources will play an increasingly important role to understanding the influence of genetic variants on disease risk, severity and progression and many drug discovery decisions. 

Suggested readings:

Nelson, M. R., Tipney, H., Painter, J. L., Shen, J., Nicoletti, P., Shen, Y., … Sanseau, P. (2015). The support of human genetic evidence for approved drug indications. Nature Genetics, 47(8), 856–860.

Plenge, R. M. (2016). Disciplined approach to drug discovery and early development. Science Translational Medicine, 8(349), 1–6.

Hurle, M. R., Nelson, M. R., Agarwal, P., & Cardon, L. R. (2016). A genomic approach to therapeutic target validation identifies a glucose-lowering GLP1R variant protective for coronary heart disease. Science Translational Medicine, 8(341).

Denny, J. C., Bastarache, L., & Roden, D. M. (2016). Phenome-Wide Association Studies as a Tool to Advance Precision Medicine. Annual Review of Genomics and Human Genetics, 17(1), 353–373.