Single nucleotide polymorphisms associated with methotrexate-induced nausea in juvenile idiopathic arthritis

Kyvsgaard, Nini; Mikkelsen, Torben Stamm; Als, Thomas D.; Christensen, Anne Estmann; Corydon, Thomas J.; Herlin, Troels

doi:10.1186/s12969-021-00539-9

Pediatric Rheumatology

Table 5 The specific haplotypes and the phenotype “MTX-intolerance”

From: Single nucleotide polymorphisms associated with methotrexate-induced nausea in juvenile idiopathic arthritis

Chr	Markers	Haplotype	F cases	F controls	Score	p-value	p-sim
1	rs1801131-rs1801133	A-C	0.348	0.402	−0.916	0.360	0.329
1	rs1801131-rs1801133	A-T	0.340	0.228	1.852	0.064	0.06
1	rs1801131-rs1801133	C-C	0.312	0.370	−0.914	0.361	0.324
1	rs1801131-rs1801133	C-T	0.000	0.000	NA	NA	NA
7	rs1045642-rs2032582	C-A	0.021	0.022	−0.048	0.962	1
7	rs1045642-rs2032582	C-G	0.401	0.435	−0.530	0.596	0.557
7	rs1045642-rs2032582	C-T	0.008	0.000	NA	NA	NA
7	rs1045642-rs2032582	T-G	0.154	0.174	−0.432	0.666	0.694
7	rs1045642-rs2032582	T-T	0.415	0.370	0.758	0.448	0.422
10	rs717620-rs2273697-rs3740066	A-A-A	0.000	0.000	NA	NA	NA
10	rs717620-rs2273697-rs3740066	A-G-A	0.201	0.250	−0.852	0.394	0.427
10	rs717620-rs2273697-rs3740066	A-G-G	0.000	NA	NA	NA	NA
10	rs717620-rs2273697-rs3740066	G-A-A	0.023	0.018	NA	NA	NA
10	rs717620-rs2273697-rs3740066	G-A-G	0.227	0.221	0.070	0.944	0.961
10	rs717620-rs2273697-rs3740066	G-G-A	0.182	0.112	1.465	0.143	0.153
10	rs717620-rs2273697-rs3740066	G-G-G	0.367	0.399	−0.466	0.641	0.639
10	rs717620-rs2273697	A-A	0.000	0.000	NA	NA	NA
10	rs717620-rs2273697	A-G	0.201	0.250	−0.852	0.394	0.36
10	rs717620-rs2273697	G-A	0.250	0.239	0.168	0.867	0.84
10	rs717620-rs2273697	G-G	0.549	0.511	0.537	0.591	0.572
10	rs2273697-rs3740066	A-A	0.021	0.017	NA	NA	NA
10	rs2273697-rs3740066	A-G	0.229	0.223	0.110	0.913	0.936
10	rs2273697-rs3740066	G-A	0.386	0.364	0.376	0.707	0.732
10	rs2273697-rs3740066	G-G	0.364	0.397	−0.526	0.599	0.587
11	rs1176744-rs1062613-rs1985242-rs1176713	G-C-A-C	0.071	0.043	0.558	0.577	0.569
11	rs1176744-rs1062613-rs1985242-rs1176713	G-C-T-T	0.029	0.008	NA	NA	NA
11	rs1176744-rs1062613-rs1985242-rs1176713	G-T-A-T	0.220	0.156	1.153	0.249	0.265
11	rs1176744-rs1062613-rs1985242-rs1176713	T-C-A-C	0.041	0.035	0.066	0.948	0.972
11	rs1176744-rs1062613-rs1985242-rs1176713	T-C-T-T	0.000	0.051	NA	NA	NA
11	rs1176744-rs1062613-rs1985242-rs1176713	T-T-A-C	0.001	NA	NA	NA	NA
11	rs1176744-rs1062613-rs1985242-rs1176713	T-T-A-T	0.029	0.063	−1.030	0.303	0.287
11	rs1176744-rs1062613-rs1985242	G-C-A	NA	0.016	NA	NA	NA
11	rs1176744-rs1062613-rs1985242	G-C-T	0.513	0.496	0.406	0.685	0.693
11	rs1176744-rs1062613-rs1985242	G-T-A	0.048	0.098	−1.430	0.153	0.153
11	rs1176744-rs1062613-rs1985242	T-C-A	0.034	0.034	−1.283	0.199	0.142
11	rs1176744-rs1062613-rs1985242	T-C-T	0.016	NA	NA	NA	NA
11	rs1176744-rs1062613-rs1985242	T-T-A	0.097	0.054	0.822	0.411	0.397
11	rs1176744-rs1062613-rs1985242	T-T-T	0.218	0.164	1.219	0.223	0.23
11	rs1062613-rs1985242-rs1176713	C-A-C	0.045	0.075	−1.052	0.293	0.276
11	rs1062613-rs1985242-rs1176713	C-A-T	0.001	NA	NA	NA	NA
11	rs1062613-rs1985242-rs1176713	C-T-T	0.030	0.077	−1.331	0.183	0.186
11	rs1062613-rs1985242-rs1176713	T-A-C	0.516	0.488	0.355	0.722	0.735
11	rs1062613-rs1985242-rs1176713	T-A-T	0.078	0.142	−1.947	0.052	0.054
11	rs1062613-rs1985242-rs1176713	T-T-T	0.015	NA	NA	NA	NA
11	rs1176744-rs1062613	G-C	0.099	0.106	−0.190	0.849	0.862
11	rs1176744-rs1062613	G-T	0.028	0.025	0.094	0.925	0.982
11	rs1176744-rs1062613	T-C	0.734	0.652	1.486	0.137	0.129
11	rs1176744-rs1062613	T-T	0.088	0.133	−1.048	0.295	0.302
11	rs1062613-rs1985242	C-A	0.034	0.084	−1.688	0.091	0.126
11	rs1062613-rs1985242	C-T	0.016	0.000	NA	NA	NA
11	rs1062613-rs1985242	T-A	0.323	0.224	1.489	0.137	0.137
11	rs1062613-rs1985242	T-T	0.038	0.070	−0.848	0.396	0.379
11	rs1985242-rs1176713	A-C	0.538	0.559	−0.078	0.937	0.953
11	rs1985242-rs1176713	A-T	0.101	0.148	−1.663	0.096	0.098
11	rs1985242-rs1176713	T-C	0.128	0.130	−0.136	0.892	0.868
11	rs1985242-rs1176713	T-T	0.734	0.652	1.488	0.137	0.126
12	rs2117032-rs4149056-rs4149081	C-C-A	0.082	0.045	0.914	0.361	0.392
12	rs2117032-rs4149056-rs4149081	C-C-G	0.000	0.000	NA	NA	NA
12	rs2117032-rs4149056-rs4149081	C-T-G	0.279	0.325	−0.596	0.551	0.554
12	rs2117032-rs4149056-rs4149081	C-T-T	0.092	0.097	0.172	0.864	0.855
12	rs2117032-rs4149056-rs4149081	T-C-A	0.014	0.022	NA	NA	NA
12	rs2117032-rs4149056-rs4149081	T-C-C	0.533	0.512	0.162	0.872	0.895
12	rs2117032-rs4149056-rs4149081	T-T-G	0.082	0.046	0.904	0.366	0.368
12	rs2117032-rs4149056	C-C	0.279	0.324	−0.593	0.553	0.566
12	rs2117032-rs4149056	C-T	0.091	0.096	0.177	0.860	0.828
12	rs2117032-rs4149056	T-C	0.547	0.535	0.039	0.969	0.984
12	rs2117032-rs4149056	T-T	0.174	0.141	0.660	0.509	0.586
12	rs4149056-rs4149081	C-A	0.014	0.022	NA	NA	NA
12	rs4149056-rs4149081	C-C	0.813	0.837	−0.490	0.624	0.681
12	rs4149056-rs4149081	C-G	0.082	0.045	0.914	0.361	0.392
12	rs4149056-rs4149081	C-T	0.000	0.000	NA	NA	NA
12	rs4149056-rs4149081	T-C	0.279	0.325	−0.596	0.551	0.554
12	rs4149056-rs4149081	T-G	0.092	0.097	0.172	0.864	0.855
12	rs4149056-rs4149081	T-T	0.014	0.022	NA	NA	NA

The haplotype-specific scores for the listed markers in association with the parent-assessed MTX-induced nausea – the methotrexate intolerance severity score
N = 118, due to missing SNP data for two patients and MISS data for one
Chr Chromosome. Markers; the SNPs in the haplotype. Haplotypes; the alleles for the SNPs in the haplotype. Cases; MTX_intolerant (n = 72). Controls; MTX_tolerant (n = 46). F_cases; Frequency of the haplotype among cases, F_controls; Frequency of the haplotype among controls. Score; the haplotype association test score for the specific haplotype. P-sim the number of times the simulated score statistics exceeds the observed divided by the total number of simulations (1000)

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