Homozygote CRIM1 variant is associated with thiopurine-induced neutropenia in leukemic patients with both wildtype NUDT15 and TPMT

Table 2 List of 12 candidate variants for thiopurine toxicity in the discovery cohort (N = 188)

SNV: risk allele	Gene symbol	SIFT score	CADD score	ExAC EAS AF	No. of variant carriers	Last-cycle 6-MP DIP (%)			Additive		Recessive
SNV: risk allele	Gene symbol	SIFT score	CADD score	ExAC EAS AF	No. of variant carriers	Carrier	Noncarrier	ANOVA p	Effect size	p^†	Effect size	p^†
rs3821169:T	CRIM1	0	25.3	0.243	88	64.41 ± 27.7	71.99 ± 27.0	0.015	− 9.07	0.0079	− 21.09	0.0248
rs191083003:T	FSIP2	0.01	26.7	3.46E−03	3	25.79 ± 21.1	69.13 ± 27.1	0.007	− 46.98	0.0033	NA	NA
rs67877771:G	IQCG	0.04	26.2	0.215	59	61.13 ± 25.3	71.79 ± 28.0	0.010	− 10.68	0.0086	− 22.55	0.2531
rs200125400:A	SLC22A5	0	32	2.39E−03	2	16.44 ± 0.7	69.00 ± 27.2	0.007	− 52.63	0.0069	NA	NA
rs141145196:A	TOP1MT	0.03	27.1	4.76E−03	2	19.46 ± 17.7	68.97 ± 27.2	0.011	− 54.90	0.0061	NA	NA
rs61758536:A	SPAG8	0	26	0.052	28	56.14 ± 26.6	70.60 ± 27.2	0.010	− 14.74	0.0087	NA	NA
rs181036640:A	DPP7	0	28.7	0.011	4	31.90 ± 28.4	69.24 ± 27.1	0.007	− 37.27	0.0071	NA	NA
rs34337292:C	OR9Q2	0	25.9	0.068	48	59.46 ± 28.7	71.52 ± 26.5	0.002	− 11.98	0.0044	− 37.44	0.0195
rs200982819:A	SLC15A3	0	29.7	0.028	7	42.40 ± 18.8	69.45 ± 27.4	0.005	− 24.41	0.0056	− 58.42	0.0340
rs144612495:T	GOLGA3	0.02	25.7	4.00E−03	2	18.16 ± 6.0	68.98 ± 27.2	0.009	− 55.00	0.0049	NA	NA
rs12587478:T	KLHL33	0	25	0.059	11	44.20 ± 27.5	69.95 ± 26.9	0.005	− 22.01	0.0034	− 17.75	0.5218
rs746000108:T	INSR	0.01	25	5.01E−04	2	18.11 ± 15.8	68.98 ± 27.2	0.009	− 50.77	0.0097	NA	NA

DIP dose intensity percentage, SIFT sorting intolerant from tolerant, CADD combined annotation-dependent depletion, EAS East Asians, AF allele frequency, ExAC Exome Aggregation Consortium, SNV single-nucleotide variant; NA not available
^†p values from multivariate linear regression analyses of additive and recessive models

ISSN: 1479-5876