Table 3.

Genes associated with opioid response at an adjusted p value ≤ 0.05.

Opioids	Outcome	Gene	All			Men			Women
			Burdenc	No. of variantsa	P valueb	Burdenc	No. of variantsa	P value b	Burdenc	No. of variantsa	P valueb
Codeine/Tramadol	Adverse reactions	FAAH	Risk	24	1.7 × 10−7	Risk	12	2.1 × 10−6	Risk	18	0.0001
		SCN1A	Risk	42	0.0002	Risk	23	0.47	Risk	26	0.0005
		NAT2	Risk	27	0.0031	Risk	15	0.0002	Risk	18	0.22
		CYP3A4	Risk	33	0.013	Risk	19	0.0001	Risk	21	0.30
	Poor pain control	TYMS	Risk	8	3.5 × 10−5	Risk	6	1.1 × 10−6	Risk	5	0.30
		CYP1A2	Risk	29	0.038	Risk	21	0.0001	Protective	16	0.83
Hydrocodone/Oxycodone	Adverse reactions	FAAH	Risk	40	7.6 × 10−5	Risk	18	1.4 × 10−10	Risk	29	0.64
	Poor pain control	SLC22A2	Risk	53	0.0017	Risk	31	9.3 × 10−6	Risk	33	0.61

Bold cells indicate results are statistically significant.

^aNumber of variants based on a functional impact filter defined as assigned CAVA impact tier of “moderate” or “high”.

^bP values ≤ 3.3 × 10⁻⁴ (Bonferroni correction) were considered statistically significant.

^cDefined by the sign of the burden test statistic, where positive values indicate genetic burden associated with increased risk.