Table 3. SKAT-O test association analysis across TPMPT and other genes involved in thiopurine toxicity.

Chr	Lbp	Rbp	Gene	Total number of samples	Fraction of individuals who carry rare variants under the MAF thresholds (MAF < 0.05)	Number of all variants defined in the group file	Number of variants defined as rare (MAF <  0.05)*
Biochemical activity (52 with TPMT value <67 and 48 with TPMT value >67)
18	33767568	33848581	MOCOS	100	0.12000	12	5
6	18130918	18148069	TPMT	100	0.10000	5	2
Tolerance (14 intolerant and 64 tolerant)
3	155588592	155654236	GMPS	78	0.12821	5	5
6	18130918	18148069	TPMT	78	0.01282	5	1
Responses (51 Responders and 13 non-responders)
5	55231311	55272085	IL6ST	64	0.10937	8	3
13	95696540	95953517	ABCC4	64	0.31250	22	9

The SKAT-O test was applied to assess the joint effect of common, rare and low frequency variants within the genes implicated in thiopurine toxicity (only significant genes are shown) on TPMT enzyme activity, tolerance and response to the drug.

^*These variants received different weights in the SKAT-O joint test. Genes are ordered by p-value.