Table 1.

Associations between germline variants and drug response

Candidate causal variant	Variant annotation	Drug name	Putative drug target	Compound clinical stage	P value	Adjusted P value	Effect size
Causal rs1800566 (lead rs12595927)	Missense variant NQO1	17-AAG	HSP90	In clinical development	2.80·10-20	3.77·10-5	−7.89·10-2
rs67038646	Intron variant FRMD4A	XL-880	MET	In clinical development	1.94·10-11	1.13·10-4	5.00·10-2
rs148617501	3′ UTR variant	SB 216763	GSK3A, GSK3B	Experimental	1.48·10-10	1.02·10-3	3.84·10-2
rs6461564	Intron variant SP4	Mitomycin C	DNA crosslinker	Clinically approved	2.27·10-9	1.26·10-2	−5.44·10-2
rs1825828	Intergenic variant	XMD8-92	MAP2K5 (ERK5)	Experimental	2.36·10-9	1.29·10-2	−2.08·10-2
rs12991665	Intron variant DPP10	Pyrimethamine	DHFR	Clinically approved	2.66·10-9	1.43·10-2	−5.81·10-2
rs56291722	Downstream gene variant (eQTL for GJA1)	CGP-082996	CDK4	Experimental	6.04·10-9	2.98·10-2	3.90·10-2
rs7919642	Intron variant CAMK1D	AZD-0530	SRC, ABL1	In clinical development	1.09·10-8	4.94·10-2	2.10·10-2
rs11710820	Intergenic variant	Vorinostat	HDAC class I, IIa, IIb, IV	Clinically approved	1.10·10-8	4.98·10-2	−8.53·10-2

Shown are candidate causal variant for nine drugs with significant germline drug response QTLs. For all instances, but 17-AAG, shown is the lead variant; For 17-AAG, the causal variant in NQO1 is known⁵². Variant annotations were obtained from the variant effect predictor⁵³. For each drug, shown is the putative target and the clinical stage