Table 4.

Genome-wide significant variants from treatment-specific GWAS for IFNβ-1b s.c

ADA	Variant	Chr.	Pos. (bp)	MA	MAF (KI)	MAF (TUM)	OR/β (Disc.)	p (Disc.)	OR/β (Repl.)	p(one-sided) (Repl.)	OR/β (Pool.)	p (Pool.)
nADA pres.	rs28366299	6	32,560,870	A	0.20	0.19	3.11OR	2.1 × 10−12	5.84OR	5.2 × 10−09	3.56OR	6.6 × 10−19
nADA titer	rs28366299	6	32,560,870	A	0.20	0.19	0.40β	1.8 × 10−16	0.52β	1.1 × 10−09	0.43β	5.3 × 10−24
nADA titer	rs9272775	6	32,610,257	C	0.22	0.23	0.38β	2.5 × 10−16	0.51β	3.2 × 10−10	0.41β	2.5 × 10−24
bADA level	rs78279385	6	32,451,758	A	0.23	0.25	0.39β	2.7 × 10−14	0.39β	2.0 × 10−06	0.39β	5.5 × 10−19
bADA level	rs9272775	6	32,610,257	C	0.22	0.23	0.39β	1.0 × 10−13	0.46β	1.1 × 10−07	0.41β	1.6 × 10−19

The top GWAS association signals that showed genome-wide significance in the discovery-stage analysis (α = 5 × 10⁻⁸) and replicated (α = 3 × 10⁻³) in the analysis of IFNβ-1b s.c.-treated patients. For nADA presence, odds ratios are provided (marked by ^OR), and for quantitative ADA measures effect sizes (marked by ^β). For detailed association statistics, including conditional analyses, correlated HLA alleles, nearby genes, eQTL results, permutation p values, and preparation-specific association results, see Additional file 12. For locus-specific Manhattan plots of each locus, see Additional file 20. For forest plots of each association, including treatment preparation-specific effects, see Additional file 21. Abbreviations: Chr. chromosome; Pos. position in base pairs (build hg19); MA minor and effect allele; MAF minor allele frequency; KI Karolinska Institutet, Sweden; TUM Technical University of Munich, Germany; OR odds ratio; β effect size; Disc discovery; Repl. replication; Pool. pooled; pres. presence