Annotating and interpreting the results of genome-wide association studies 
(GWAS) remains challenging. Assigning function to genetic variants as expression 
quantitative trait loci is an expanding and useful approach, but focuses 
exclusively on mRNA rather than protein levels. Many variants remain without 
annotation. To address this problem, we measured the steady state abundance of 
441 human signaling and transcription factor proteins from 68 Yoruba HapMap 
lymphoblastoid cell lines to identify novel relationships between 
inter-individual protein levels, genetic variants, and sensitivity to 
chemotherapeutic agents. Proteins were measured using micro-western and reverse 
phase protein arrays from three independent cell line thaws to permit mixed 
effect modeling of protein biological replicates. We observed enrichment of 
protein quantitative trait loci (pQTLs) for cellular sensitivity to two commonly 
used chemotherapeutics: cisplatin and paclitaxel. We functionally validated the 
target protein of a genome-wide significant trans-pQTL for its relevance in 
paclitaxel-induced apoptosis. GWAS overlap results of drug-induced apoptosis and 
cytotoxicity for paclitaxel and cisplatin revealed unique SNPs associated with 
the pharmacologic traits (at p<0.001). Interestingly, GWAS SNPs from various 
regions of the genome implicated the same target protein (p<0.0001) that 
correlated with drug induced cytotoxicity or apoptosis (p ≤ 0.05). Two genes 
were functionally validated for association with drug response using siRNA: 
SMC1A with cisplatin response and ZNF569 with paclitaxel response. This work 
allows pharmacogenomic discovery to progress from the transcriptome to the 
proteome and offers potential for identification of new therapeutic targets. 
This approach, linking targeted proteomic data to variation in pharmacologic 
response, can be generalized to other studies evaluating genotype-phenotype 
relationships and provide insight into chemotherapeutic mechanisms.