The burden of rare variants in DPYS gene is a novel predictor of the risk of developing severe fluoropyrimidine-related toxicity

Table 2 Gene and pathway-level SKAT output

Common and rare variants (SKATjoint)^a
Gene (HGNC)	crude.P	BH.P	Bonf.P
All variants
ABCB4	0.041	0.196	1
ABCC3	0.020	0.136	0.882
ABCC4	0.053	0.196	1
ABCC5	0.021	0.136	0.943
CYP2A6	0.010	0.136	0.432
*DPYS*	0.001	0.024	0.024
NR1I3	0.049	0.196	1
PPARD	0.022	0.136	0.954
SLC22A7	0.015	0.136	0.645
VDR	0.003	0.066	0.131
DLG5	0.052	0.196	1
RRM2	0.044	0.196	1
All variants deleterious
ABCB4	0.0168	0.3019	0.604
NR1H3	0.0336	0.4036	1
*PPARD*	0.0011	0.0389	0.039
VDR	0.0497	0.4475	1
3’UTR/5’UTR
ABCC5	0.030	0.304	1
CES1	0.023	0.304	0.925
DPYS	0.002	0.072	0.072
MTHFR	0.045	0.366	1
VDR	0.018	0.304	0.754
3’UTR/5’UTR deleterious
*PPARD*	0.001	0.022	0.022
Missense
ABCB4	0.010	0.306	0.376
CYP2A6	0.051	0.306	1
ENOSF1	0.045	0.306	1
NR1H3	0.048	0.306	1
RRM2	0.018	0.306	0.645
VDR	0.050	0.306	1
Missense deleterious
ABCB4	0.017	0.278	0.520
NR1H3	0.048	0.385	1
RRM2	0.018	0.278	0.555
VDR	0.050	0.385	1

Common and rare variants (SKATjoint)^a
Subpathway	crude.P	BH.P	Bonf.P
All variants
Nuclear Receptor	0.004	0.018	0.033
Membrane transporter	0.004	0.018	0.037
All variants deleterious
Nuclear receptor	0.008	0.075	0.075
3’UTR/5’UTR
Nuclear receptor	0.049	0.212	0.444
3’UTR/5’UTR deleterious
Nuclear receptor	0.016	0.095	0.095
Missense
Nuclear receptor	0.044	0.229	0.395
Missense deleterious
–

Only the associations with crude P < 0.05 are reported. Association with also Bonferroni P < 0.05 is evidenced in bold
^aP values were estimated adjusting for sex, age, cancer site, treatment setting, and fluoropyrimidines
The variants are classified as common (MAF ≥ 1%) and rare (MAF < 1%). Novel variants (MAF not registered; absence of rs ID in dbSNP database) are included in the rare

ISSN: 1479-7364