C4 long gene (20.4kb)

1. STK19P TNXA STK19 C4 CYP21 C4 CYP21 TNXB STK19P STK19P TNXA TNXA STK19 C4 CYP21 C4 CYP21 C4 CYP21 TNXB STK19P STK19P STK19P TNXA TNXA TNXA STK19 C4 CYP21 C4 CYP21 C4 CYP21 C4 CYP21 TNXB Supplementary Figure 1 a SNP rs3130342 [G/T] STK19 C4 CYP21 TNXB b Exon26, amino acids 1101-1106 C4 short gene (14.1kb) C4A gene C4 long gene (20.4kb) C4B gene HERV-K(C4) Supplementary Figure 1a The pattern of C4 CNV and the position of SNP rs3130342 were shown. This CNV region is reported to have variations of one, two, three or four repeats. Telomeric end is STK19 gene and centromeric end is TNXB gene. Within repeat sequence, C4 and CYP21 are multiplicated as complete genes, whereas STK19 and TNX were truncated to become pseudogenes, STK19P and TNXA, respectively. SNP rs3130342 is located at 5’-UTR of TNXB gene and is not included in the repeat sequence. b There are four major variants of C4 genes. Left figure shows that C4 long gene has insertion sequence named HERV-K(C4) in intron 9, whereas C4 short gene does not. C4A and C4B variants differ by only 4 amino acids at position 1101-1106, as shown in right figure.

2. Supplementary Figure 2 b 1 2 3 4 5 6 7 8 9 y = -0.0316x + 0.02 a R2 = 0.0391 0.8 RP1-C4L RP1-C4S 0.6 RP2-C4L 0.4 RP2-C4S 0.2 CT 0 RP1-C4L RP1-C4S -0.2 2: 0: 0: 1 2: 0: 0: 2 2: 0: 3: 0 2: 0: 1: 0 2: 0: 2: 0 2: 0: 0: 2 2: 0: 1: 1 2: 0: 1: 1 2: 0: 1: 1 RP2-C4L RP2-C4S -0.4 -0.6 -1 -0.5 0 0.5 1 1.5 TNXB log ng of Genomic DNA TNXA TNXB: TNXA 2:2 2:3 2:1 2:2 2:2 2:2 2:1 2:2 2:2 c 2.5 2 1.5 2-Ct (qPCR) 1 R2 = 0.996 0.5 0 0 0.5 1 1.5 2 2.5 Gene copy number (Southern)

3. Supplementary table 1. Characteristics of cohorts a Age of onset for SLE patients, and age at drawing DNA samples for control patients. Supplementary table 2. Probes and primers for qPCR

4. Supplementary table 3. Association of SNP rs1009382 from genome-wide study a Odds ratio of allele count model (A or G). b Fisher’s exact test of allele count model. Supplementary table 4. CNV analysis on female subgroup A B a Results of Wilcoxon rank sum test comparing the copy numbers of Case1 and Case 2 with Control 2. The significant level alpha=0.025 for all the tests. * indicated p values below significant level.

5. Supplementary Table 5. Stratified analysis of rs3130342 with HLA-DRB1*1501 allele. a Odds ratio of recessive effect (GG or GT+TT). b Fisher’s exact test of recessive effect model. c Those who have at lease one HLA-DRB1*1501 allele. d Those who have no HLA-DRB1*1501 allele at either chromosome.