The proteasome-inhibitor bortezomib was introduced into the treatment of 
multiple myeloma more than a decade ago. It is clinically beneficial, but 
peripheral neuropathy (PNP) is a side effect that may limit its use in some 
patients. To examine the possible genetic predisposing factors to PNP, we 
performed a genome-wide association study on 646 bortezomib-treated German 
multiple myeloma patients. Our aim was to identify genetic risk variants 
associated with the development of PNP as a serious side effect of the 
treatment. We identified 4 new promising loci for bortezomib-induced PNP at 
4q34.3 (rs6552496), 5q14.1 (rs12521798), 16q23.3 (rs8060632), and 18q21.2 
(rs17748074). Even though the results did not reach genome-wide significance 
level, they support the idea of previous studies, suggesting a genetic basis for 
neurotoxicity. The identified single nucleotide polymorphisms map to genes or 
next to genes involved in the development and function of the nervous system 
(CDH13, DCC, and TENM3). As possible functional clues, 2 of the variants, 
rs12521798 and rs17748074, affect enhancer histone marks in the brain. The 
rs12521798 may also impact expression of THBS4, which affects specific signal 
trasduction pathways in the nervous system. Further research is needed to 
clarify the mechanism of action of the identified single nucleotide 
polymorphisms in the development of drug-induced PNP and to functionally 
validate our in silico predictions.