Table 4.

Top-associated variant and replication test statistics for each of the clinical strata and drug-specific or drug class-specific analyses

				Discovery cohort			Replication cohort			Combined
Phenotypes	SNP set	SNP	Nearest gene	Na	P-value	OR (95%CI)	Nb	P-value	OR (95%CI)	N	P-value
All DILI	ADME	rs3740065	ABCC2	783	2.6×10−5	1.45 (1.22–1.72)	304	0.49	0.90 (0.68–1.20)	1087	1.9×10−3
Cholestatic	AI and GWAS	rs2476601	PTNP22	187	5.4×10−7	2.20 (1.62–3.00)	105	0.26	0.74 (0.44–1.24)	292	8.0×10−4
Hepatocellular	AI	rs7574865	STAT4	256	4.5×10−4	1.45 (1.18–1.79)	168	0.011	1.39 (1.08–1.78)	424	1.5×10−5
Diclofenacc	GWAS	rs17036170	PPARG	30	1.0×10−8	11.3 (4.9–25.9)	26	0.088	3.59 (0.83–15.6)	56	2.0×10−8
Fluoroquinolones	ADME	rs17862876	UGT1A	12	3.4×10−5	11.6 (3.6–37.4)	10	1.00	NA	22	8.0×10−4
NSAIDs	GWAS	rs9376256	IL22RA2	68	6.7×10−8	3.42 (2.19–5.34)	12	0.42	0.44 (0.06–3.23)	80	1.0×10−4
Statins	AI	rs7574865	STAT4	27	4.9×10−5	3.35 (1.87–6.00)	16	0.58	0.77 (0.31–1.91)	43	3.5×10−3

ADME, ADME SNP-restricted analyses; AI, autoimmune disease SNP-restricted; GWAS, column ‘SNP set’ indicates whether the target SNP was brought forward for replication on the basis of the results of the genome-wide analysis.

ADME, absorption, distribution, metabolism, and excretion; DILI, drug-induced liver injury; GWAS, genome-wide association study; OR, odds ratio; SNP, single-nucleotide polymorphism; STAT4, signal transducer and activator of transcription 4.

^aN indicates number of case samples compared with 3001 population controls from the Population Reference Sample and 1958 British Birth Cohort.

^bN indicates number of case samples compared with 2249 population controls from the National Blood Service cohort.

^cDiclofenac-DILI samples for replication were genotyped specifically for rs17036170 and were not included in omnibus or injury-type-specific tests.