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Table 5 Selected significant HLA alleles and haplotypes

From: Treatment- and population-specific genetic risk factors for anti-drug antibodies against interferon-beta: a GWAS

ADA Allele/HT AF (KI) AF (TUM) OR/β (Disc.) p (Disc.) OR/β (Repl.) p(one-sided) (Repl.) OR/β (Pool.) p (Pool.)
All preparations: risk alleles
 bADA levels HLA-DQA1*01:02 0.42 0.36 0.18β 1.6 × 10−08 0.17β 3.7 × 10−04 0.17β 4.8 × 10−11
 bADA levels B7-DQ6 0.18 0.17 0.17β 8.6 × 10−06 0.21β 3.8 × 10−04 0.18β 2.7 × 10−08
All preparations: protective alleles
 bADA levels DR3-DQ2 0.13 0.12 − 0.23β 9.6 × 10−08 − 0.21β 6.7 × 10−04 − 0.23β 5.0 × 10−10
IFNβ-1a s.c.: risk alleles
 nADA pres. DR15-DQ6 0.34 0.30 2.73OR 3.1 × 10−14 3.41OR 1.5 × 10−07 2.89OR 7.4 × 10−20
 nADA titer DR15-DQ6 0.34 0.30 0.36β 1.3 × 10−15 0.32β 2.3 × 10−07 0.35β 3.6 × 10−21
 bADA levels DR15-DQ6 0.34 0.30 0.44β 6.8 × 10−15 0.45β 4.4 × 10−08 0.44β 3.5 × 10−21
IFNβ-1a s.c.: protective alleles
 nADA pres. DR3-DQ2 0.13 0.12 0.40OR 9.1 × 10−07 0.29OR 4.0 × 10−04 0.37OR 3.7 × 10−09
 nADA titer DR3-DQ2 0.13 0.12 − 0.31β 8.6 × 10−08 − 0.28β 5.0 × 10−04 − 0.30β 3.4 × 10−10
 bADA levels DR3-DQ2 0.13 0.12 − 0.41β 2.1 × 10−08 − 0.40β 1.5 × 10−04 − 0.41β 2.5 × 10−11
IFNβ-1b s.c.: risk alleles
 nADA pres. HLA-DRB1*04:01 0.09 0.07 6.82OR 3.4 × 10−13 14.7OR 1.7 × 10−07 7.95OR 1.4 × 10−18
 nADA pres. DR4-DQ3 0.07 0.05 6.23OR 1.2 × 10−09 14.7OR 6.1 × 10−06 7.35OR 1.5 × 10−13
 nADA titer HLA-DRB1*04:01 0.09 0.07 0.56β 4.1 × 10−15 0.56β 9.2 × 10−06 0.56β 3.7 × 10−19
 nADA titer DR4-DQ3 0.07 0.05 0.50β 1.6 × 10−09 0.54β 1.3 × 10−04 0.51β 1.9 × 10−12
 bADA levels HLA-DRB1*04:01 0.09 0.07 0.62β 4.6 × 10−15 0.61β 1.8 × 10−06 0.62β 8.7 × 10−20
 bADA levels DR4-DQ3 0.07 0.05 0.56β 4.9 × 10−10 0.53β 2.2 × 10−04 0.56β 9.0 × 10−13
  1. Selected four-digit HLA alleles and extended haplotypes that were significantly associated (p < 3 × 10−4) with an ADA measurement and replicated (pone-sided < 1 × 10−3). Alleles that are part of one of the listed extended haplotypes and showed a similar or weaker association than the haplotypes and which did not remain significant when conditioning for the haplotypes are not displayed separately. For nADA presence, odds ratios are provided (marked by OR), and for quantitative ADA measures effect sizes (marked by β). For a detailed table of all results, see Additional file 22. For forest plots of each association, including treatment preparation-specific effects, see Additional files 14, 19, and 21. HT haplotype; AF allele frequency; KI Karolinska Institutet, Sweden; TUM Technical University of Munich, Germany; β effect size; OR odds ratio; Disc discovery; Repl. replication; Pool. pooled; pres.presence. Abbreviations of the haplotypes: B7-DQ6, HLA-B*07:02 + HLA-DRB1*15:01 + HLA-DQA1*01:02 + HLA-DQB1*06:02; DR15-DQ6, HLA-DRB1*15:01 + HLA-DQA1*01:02 + HLA-DQB1*06:02; DR3-DQ2, HLA-DRB1*03:01 + HLA-DQA1*05:01 + HLA-DQB1*02:01; DR4-DQ3, HLA-DRB1*04:01 + HLA-DQA1*03:01 + HLA-DQB1*03:02