Table 2.

Effect of previously reported variants on placebo-arm outcome

A. Response at the conclusion of the trial
Pathway	Gene	SNP	Rheumatoid arthritis		Asthma		Meta-analysis
			P	OR	P	OR	P(R)	OR(R)
Dopamine	COMT	rs4680	0.4904	1.118	0.9495	0.989	0.6390	1.058
	DBH	rs2873804	0.6423	0.929	0.7345	1.059	0.9161	0.988
	DRD3	rs6280	0.4189	0.872	0.0148	0.593	0.1075	0.735
	BDNF	rs6265	0.4131	1.184	0.3074	1.248	0.1950	1.214
Serotonin	TPH2	rs4570625	0.9836	1.004	0.0089	1.761	0.3299	1.315
	SLC6A4	rs4251417	0.4387	0.819	0.9683	0.990	0.5643	0.900
	HTR2A	rs2296972	0.1972	1.264	0.8436	1.041	0.2747	1.160
		rs622337	0.1678	1.282	0.9128	1.023	0.2685	1.162
Opioid	OPRM1	rs510769	0.9599	0.991	0.6785	1.085	0.8145	1.031
Endocannabinoid	FAAH	rs324420	0.9631	1.008	0.9102	0.976	0.9694	0.995

B. Placebo response in the first month of the trial
Pathway	Gene	SNP	Rheumatoid arthritis		Asthma		Meta-analysis
			P	OR	P	OR	P(R)	OR(R)
Dopamine	COMT	rs4680	0.9951	0.999	0.9311	1.015	0.9537	1.0068
	DBH	rs2873804	0.4087	1.144	0.4585	0.8897	0.9638	1.0057
	DRD3	rs6280	0.5616	1.105	0.0037	0.5571	0.4935	0.791
	BDNF	rs6265	0.8789	0.9686	0.9986	0.9996	0.9134	0.9841
Serotonin	TPH2	rs4570625	0.2054	1.267	0.2058	1.298	0.0740	1.2809
	SLC6A4	rs4251417	0.2478	1.348	0.6478	0.894	0.6773	1.0891
	HTR2A	rs2296972	0.255	1.228	0.4415	0.8604	0.8419	1.0361
		rs622337	0.242	1.232	0.4174	0.8524	0.8542	1.0344
Opioid	OPRM1	rs510769	0.0883	0.7355	0.9285	0.9833	0.2508	0.8465
Endocannabinoid	FAAH	rs324420	0.1314	1.316	0.2669	1.248	0.0626	1.2847

P-values and odds ratios for each variant’s logistic association with placebo response for each disease and a random-effect meta-analysis. (A) Placebo response observed at the conclusion of each trial, which varied by trial but ranged 24–52 weeks. (B) Placebo response recorded in the first month of treatment. A Bonferroni-corrected P-value threshold of 0.0025 was used to determine the significance. After correction, none of the previously reported variants showed significance in either disease or in the meta-analysis