A genome-wide association study identifies vitiligo

Transcription

1 A genome-wide association study identifies vitiligo susceptibility loci at MHC and 6q27 Supplementary Materials Index Supplementary Figure 1 The principal components analysis (PCA) of 2,546 GWAS samples Supplementary Figure 2 Conditional logistic regression analysis for 70 SNPs in MHC region Supplementary Figure 3 The scatter plot of the association evidences within ZMIZ1 at 10q22 for vitiligo Supplementary Table 1 Results of conditional logistic regression analysis for 70 SNPs in MHC region Supplementary Table 2a Results of association analysis for 11 top MHC SNPs in GWAS Supplementary Table 2b Results of haplotype analysis for 11 top MHC SNPs in GWAS Supplementary Table 3 Results of association analysis for 32 SNPs in the GWAS and Replication 1 Supplementary Table 4 Association analysis for candidate loci/variants of vitiligo and autoimmune diseases in GWAS dataset

2 a b c d

3 e f g h Supplementary Figure 1 The principal components analysis (PCA) of 2,546 GWAS samples. (a-d) The PCA of 2,546 samples and 206 reference DNA samples form the HapMap. Cases are in red, controls are in green, CHB samples are in violet, JPT samples are in blue, CEU samples are in yellow and YRI samples are in brown. (e-h) The pair-wise PCA of 2,546 participant samples (1,117 cases, 1,429 healthy controls). The red points are the cases, and the green points are the controls.

4 a b c Supplementary Figure 2 Conditional logistic regression analysis for 70 SNPs in MHC region. The P values ( log 10 P) shown as in y-axis were plotted against their map positions (x-axis). The color of each SNP spot reflects its r 2 with the top SNP, changing from red to white. Estimated recombination rates were plotted in light blue. a. The 70 SNPs with P values of Cochran-Armitage trend test less than ; b. After controlling for the effect of rs ; c. After controlling for the effect of rs and rs

5 Supplementary Figure 3 The scatter plot of the association evidences within ZMIZ1 at 10q22 for vitiligo. The P values ( log 10 P) shown as in y-axis were plotted against their map positions (x-axis). The color of each SNP spot reflects its r 2 with the top SNP, changing from red to white. Estimated recombination rates were plotted in light blue.

6 Supplementary Table 1 Results of conditional logistic regression analysis for 70 SNPs in MHC region Gene SNP BP A1 F_A F_U P trend OR Controlling rs Controlling rs and rs P OR P OR HLA-H rs A E E E TRIM31 rs G E E E TRIM15 rs A E E E TRIM26 rs C E E E TRIM26 rs A E E E RPP21 rs A E E E RPP21 rs C E E E RPP21 rs A E E E LOC rs C E E E LOC rs G E E E LOC rs G E E E LOC rs A E E E LOC rs G E E E LOC rs G E E E HLA-E rs A E E E LOC rs A E E E LOC rs A E E E LOC rs A E E E LOC rs A E E E LOC rs G E E E LOC rs A E E E LOC rs G E E E LOC rs G E E E LOC rs A E E E LOC rs G E E E LOC rs A E E E LOC rs G E E E LOC rs A E E E LOC rs C E E E LOC rs C E E E

7 LOC rs A E E E C6orf134 rs A E E E IER3 rs A E E E DDR1 rs G E E E DDR1 rs A E E E DDR1 rs A E E E GTF2H4 rs G E E E DPCR1 rs A E E E LOC rs A E E E LOC rs C E E E CCHCR1 rs A E E E CCHCR1 rs T E E E POU5F1 rs A E E E POU5F1 rs G E E E HCG27 rs G E E E HCG27 rs A E E E HLA-C rs C E E E HLA-C rs A E E E HLA-C rs A E E NA NA HLA-C rs G E E E HLA-C rs A E E E HCP5 rs G E E E BAT1 rs G E E E NEU1 rs A E E E SLC44A4 rs A E NA NA NA NA TNXB rs A E E E TNXB rs A E E E TNXB rs A E E E TNXB rs G E E E FKBPL rs C E E E EGFL8 rs A E E E EGFL8 rs G E E E AGPAT1 rs G E E E

8 AGPAT1 rs A E E E RNF5 rs A E E E NOTCH4 rs A E E E NOTCH4 rs A E E E HLA-DRB1 rs G E E E HLA-DQA1 rs G E E E HLA-DQA1 rs G E E E

9 Supplementary Table 2a Results of association analysis for 11 top MHC SNPs in GWAS Gene SNP BP A1 F_A F_U P trend OR HLA-C rs C E HLA-C rs A E HLA-C rs A E HLA-C rs G E HLA-C rs A E SLC44A4 rs A E NOTCH4 rs A E NOTCH4 rs A E HLA-DRB1 rs G E HLA-DQA1 rs G E HLA-DQA1 rs G E Supplementary Table 2b Results of haplotype analysis for 11 top MHC SNPs in GWAS Haoplype F_A F_U HAPLOTYPE Frequency OR Chi-Square P H AGAAGGCGAAC E-08 H AGGGGGCGAAC E-01 H AGGAGGCGAAC E-01 H CGGGGGCGAAC E-02 H CAGGAAAAGGG E-09 H CAGGAGCGAAC E-01 H CAGGAGCGGGG E-02

10 Supplementary Table 3 Results of association analysis for 32 SNPs in the GWAS and Replication 1 GWAS GWAS using reference control Replication 1 (Sequenom) Minor CHR SNP BP MAF OR(95%CI) P HWE P trend MAF OR P HWE P trend MAF OR(95%CI) P HWE P trend Allele Case Control Control Case Control 1 rs C ( ) E E ( ) E-01 1 rs A ( ) E E ( ) E-01 2 rs C ( ) E E ( ) E-01 2 rs G ( ) E E ( ) E-01 2 rs A ( ) E E ( ) E-01 2 rs A ( ) E E ( ) E-01 2 rs T ( ) E E ( ) E-01 2 rs A ( ) E E ( ) E-01 3 rs G ( ) E E ( ) E-01 3 rs G ( ) E E ( ) E-01 3 rs T ( ) E E ( ) E-01 6 rs T ( ) E E ( ) E-09 6 rs C ( ) E E ( ) E-08 6 rs C ( ) E E-06 failed 7 rs C ( ) E E ( ) E-02 8 rs T ( ) E E ( ) E-01 8 rs T ( ) E E ( ) E-01 8 rs T ( ) E E-05 failed 9 rs C ( ) E E ( ) E rs C ( ) E E ( ) E rs C ( ) E E-06 failed 10 rs T ( ) E E ( ) E rs T ( ) E E ( ) E rs C ( ) E E ( ) E rs T ( ) E E ( ) E rs A ( ) E E ( ) E-01

11 19 rs G ( ) E E ( ) E rs G ( ) E E ( ) E rs G ( ) E E ( ) E rs G ( ) E E ( ) E rs C ( ) E E ( ) E rs C ( ) E E ( ) E-01 Reference control: The samples were genotyped in a series of GWAS of various diseases in Chinese Han population, including psoriasis, systemic lupus erythematosus, leprosy, atopic dermatitis, and esophageal cancer.

12 Supplementary Table 4 Association analysis for candidate loci/variants of vitiligo and autoimmune diseases in GWAS dataset CHR SNP BP A1 F_A F_U P trend OR P HWE Disease/Trait Region Reported Gene(s) 1 rs A E E-02 Vitiligo 1p36.23 RERE 1 rs G E E-03 Vitiligo 1p36.23 RERE 1 rs G E E-02 Vitiligo 1p36.23 RERE 1 rs * A E E-01 Vitiligo 1p31.3-p32.2 FOXD3 1 rs A E E+00 Vitiligo 1p13.2 PTPN22 1 rs # C E E-01 Vitiligo 1q31-q32 IL10 1 rs G E E-01 Vitiligo 1q31-q32 IL10 2 rs * C E E-01 Vitiligo 2p16.3 FBXO11 2 rs # G E E-02 Vitiligo 2q33 CTLA4 3 rs * G E E-01 Vitiligo 3p14.1-p12.3 MITF 3 rs G E E-01 Vitiligo 3q28 LPP 3 rs C E E+00 Vitiligo 3q28 LPP 3 rs A E E-01 Vitiligo 3q28 LPP 3 rs A E E+00 Vitiligo 3q28 LPP 4 rs * A E E+00 Vitiligo 4q11-q12 KIT 5 rs # G E E-01 Vitiligo 5q22.1 TSLP 6 rs8643 # G E E-02 Vitiligo 6p24.3 TXNDC5 6 rs5370 # A E E-02 Vitiligo 6p24.1 EDN1 6 rs * G E E-01 Vitiligo 9p23 TYRP1 6 rs # C E E-01 Vitiligo 7p13 CAMK2B,NUDCD3 6 rs # A E E-01 Vitiligo 6q25.1 ESR1 6 rs # A E E-01 Vitiligo 6q25.1 ESR1 6 rs A E E-01 Vitiligo 6q25.1 ESR1 6 rs A E E+00 Vitiligo 6q27 SMOC2 6 rs C E E-01 Vitiligo 6q27 SMOC2 6 rs G E E+00 Vitiligo 6q27 SMOC2 9 rs # G E E-02 Vitiligo 9q22 C9orf3 10 rs G E E-01 Vitiligo 10p15.1 IL2RA 10 rs C E E-01 Vitiligo 10p15.1 IL2RA 10 rs A E E-01 Vitiligo 10p15.1 IL2RA RBM17 10 rs G E E-01 Vitiligo 10p15.1 RBM17

13 10 rs G E E-01 Vitiligo 10p15.1 RBM17 PFKB3 10 rs G E E-01 Vitiligo 10p15.1 RBM17 PFKB3 10 rs A E E-01 Vitiligo 10p15.1 RBM17 PFKB3 10 rs A E E-01 Vitiligo 10p15.1 RBM17 PFKB3 10 rs # A E E-01 Vitiligo 10q11.2-q21 MBL2 11 rs # A E E-01 Vitiligo 11p13 CAT 11 rs # A E E-01 Vitiligo 11p13 CAT 11 rs A E E+00 Vitiligo 11q14.3 TYR 11 rs G E E-01 Vitiligo 11q14.3 TYR 11 rs G E E-01 Vitiligo 11q14.3 TYR 11 rs C E E-01 Vitiligo 11q14.3 TYR 11 rs A E E+00 Vitiligo 11q14.3 TYR 11 rs G E E-01 Vitiligo 11q14.3 TYR 12 rs # C E E-02 Vitiligo 12q12-q14 VDR 13 rs * A E E-01 Vitiligo 13q32.1 TYRP2 14 rs G E E-01 Vitiligo 14q12 GZMB 14 rs A E E-01 Vitiligo 14q12 GZMB 14 rs * A E E-01 Vitiligo 14q22.1-q22.2 GCH1 16 rs * A E E-01 Vitiligo 16q24.3 MC1R 17 rs G E E-01 Vitiligo 17p13 NLRP1 17 rs * G E E-01 Vitiligo 17q23 ACE 20 rs * G E E-01 Vitiligo 20q11.2-q12 ASIP 21 rs A E E+00 Vitiligo 21q22.3 UBASH3A 21 rs A E E-01 Vitiligo 21q22.3 UBASH3A 21 rs * A E E-02 Vitiligo 21q22.3 AIRE 22 rs A E E-01 Vitiligo 22q11.2 COMT 22 rs # G E E-01 Vitiligo 22q12 XBP1 22 rs C E E-02 Vitiligo 22q13.1 C1QTNF6 22 rs A E E-01 Vitiligo 22q13.1 C1QTNF6 1 rs A E E-01 Ulcerative colitis 1p36.13 RNF186 1 rs G E E-01 Ulcerative colitis 1p36.13 OTUD3, PLA2G2E 1 rs G E E+00 Ulcerative colitis 1p36.12 Intergenic 1 rs C E E-01 Ulcerative colitis 1p31.3 IL23R

14 1 rs G E E-01 Ulcerative colitis 1q23.3 FCGR2A 6 rs A E E-01 Ulcerative colitis 6p21.33 HLA 6 rs A E E-01 Ulcerative colitis 6p21.32 Intergenic 7 rs A E E-01 Ulcerative colitis 7q31.1 SLC26A3 7 rs A E E-02 Ulcerative colitis 7q31.1 Intergenic 7 rs A E E-01 Ulcerative colitis 7q31.1 multiple gene 7 rs C E E+00 Ulcerative colitis 7q31.1 multiple gene 7 rs A E E-01 Ulcerative colitis 7q31.1 multiple gene 9 rs G E E-01 Ulcerative colitis 9p24.1 multiple gene 9 rs G E E-01 Ulcerative colitis 9q21.32 Intergenic 9 rs A E E-01 Ulcerative colitis 9q34.3 CARD9 12 rs A E E-01 Ulcerative colitis 12q15 multiple gene 12 rs G E E+00 Ulcerative colitis 12q15 IL26 13 rs G E E-02 Ulcerative colitis 13q12.13 USP12 1 rs A E E+00 Type 1 diabetes 1p22.3 EDG7 1 rs A E E-01 Type 1 diabetes 1q32.1 IL10 2 rs G E E-01 Type 1 diabetes 2p25.1 Intergenic 2 rs A E E-01 Type 1 diabetes 2q24.2 IFIH1 4 rs A E E+00 Type 1 diabetes 4p15.2 Intergenic 4 rs G E E-01 Type 1 diabetes 4q27 IL2 5 rs G E E-01 Type 1 diabetes 5p13.2 CAPSL 6 rs A E E-01 Type 1 diabetes 6q15 BACH2 6 rs A E E+00 Type 1 diabetes 6q22.32 C6orf173 7 rs G E E-01 Type 1 diabetes 7p15.2 Intergenic 9 rs A E E-01 Type 1 diabetes 9p24.2 GLIS3 10 rs A E E-01 Type 1 diabetes 10p15.1 IL2RA 10 rs G E E-01 Type 1 diabetes 10q23.31 C10orf59 11 rs A E E-01 Type 1 diabetes 11p15.5 INS 11 rs A E E-01 Type 1 diabetes 11p15.5 INS 12 rs A E E-01 Type 1 diabetes 12p13.31 NR 12 rs A E E-01 Type 1 diabetes 12p13.31 NR 12 rs A E E-01 Type 1 diabetes 12p13.31 CD69 12 rs C E E-01 Type 1 diabetes 12q13.2 multiple gene

15 12 rs A E E+00 Type 1 diabetes 12q24.12 SH2B3 12 rs G E E+00 Type 1 diabetes 12q24.13 C12orf30 14 rs A E E-01 Type 1 diabetes 14q24.1 Intergenic 14 rs A E E-01 Type 1 diabetes 14q32.2 Intergenic 15 rs A E E-01 Type 1 diabetes 15q14 RASGRP1 16 rs A E E-01 Type 1 diabetes 16p13.13 KIAA rs A E E-01 Type 1 diabetes 16p11.2 IL27 16 rs C E E-01 Type 1 diabetes 16q23.1 Intergenic 17 rs G E E-01 Type 1 diabetes 17q12 ORMDL3 18 rs G E E-01 Type 1 diabetes 18p11.21 PTPN2 18 rs A E E-01 Type 1 diabetes 18q22.2 CD rs G E E-01 Type 1 diabetes 19q13.32 Intergenic 21 rs A E E+00 Type 1 diabetes 21q22.3 UBASH3A 21 rs G E E-01 Type 1 diabetes 21q22.3 UBASH3A 22 rs G E E-01 Type 1 diabetes 22q12.2 Intergenic 1 rs A E E+00 SLE 1p31.1 NEGR1 1 rs A E E-01 SLE 1q25.1 TNFSF4 1 rs A E E-01 SLE 1q25.1 Intergenic 2 rs G E E-01 SLE 2p22.3 RASGRP3 2 rs A E E-01 SLE 2q32.3 STAT4 2 rs A E E-01 SLE 2q32.3 STAT4 3 rs C E E-01 SLE 3p14.3 PXK 4 rs A E E-01 SLE 4q24 BANK1 5 rs A E E+00 SLE 5p12 GHR 5 rs G E E-01 SLE 5q33.1 TNIP1 6 rs A E E+00 SLE 6p21.33 HLA region 6 rs A E E-01 SLE 6p21.32 HLA-DRB1 6 rs G E E+00 SLE 6q21 PRDM1, ATG5 7 rs C E E-01 SLE 7p12.2 IKZF1 7 rs A E E-01 SLE 7q11.23 NR 7 rs A E E-01 SLE 7q32.1 IRF5 7 rs G E E+00 SLE 7q32.1 IRF5, TNPO3 7 rs A E E+00 SLE 7q32.1 IRF5, TNPO3

16 8 rs A E E-01 SLE 8p23.1 BLK 8 rs G E E-01 SLE 8p23.1 C8orf13, BLK 9 rs A E E+00 SLE 9q34.13 NTNG2 10 rs A E E-01 SLE 10q11.22 LRRC18, WDFY4 11 rs A E E+00 SLE 11p15.5 KIAA rs G E E-01 SLE 11q23.3 NR 11 rs A E E-01 SLE 11q24.3 ETS1 12 rs A E E-01 SLE 12q24.32 SLC15A4 16 rs G E E-01 SLE 16p11.2 NR 16 rs A E E-01 SLE 16p11.2 NR 16 rs A E E+00 SLE 16p11.2 ITGAM 16 rs C E E-01 SLE 16p11.2 ITGAM 16 rs G E E+00 SLE 16p11.2 ITGAM, ITGAX 17 rs A E E-01 SLE 17p12 Intergenic 18 rs A E E-01 SLE 18q22.3 SOCS6 22 rs C E E-01 SLE 22q11.21 HIC2, UBE2L3 1 rs G E E-01 Rheumatoid arthritis 1p36.32 MMEL1-TNFRSF14 2 rs A E E-01 Rheumatoid arthritis 2p16.1 REL 2 rs C E E-01 Rheumatoid arthritis 2q33.2 CTLA4 6 rs G E E-01 Rheumatoid arthritis 6p21.32 HLA-DRB1 6 rs G E E-01 Rheumatoid arthritis 6p21.32 HLA-DQA1, HLA-DQA2 8 rs G E E-01 Rheumatoid arthritis 8p23.1 BLK 9 rs A E E-01 Rheumatoid arthritis 9q33.2 TRAF1, C5 9 rs G E E-01 Rheumatoid arthritis 9q34 TRAF1-C5 18 rs C E E-01 Rheumatoid arthritis 18q23 SALL3 21 rs C E E-01 Rheumatoid arthritis 21q22.3 NR 1 rs A E E+00 Psoriasis 1p31.3 IL23R 1 rs A E E-01 Psoriasis 1q21.3 LCE3D, LCE3A 5 rs A E E-01 Psoriasis 5q31.1 IL13 5 rs A E E-01 Psoriasis 5q33.3 IL12B 6 rs G E E-01 Psoriasis 6p21.33 HLA-C 6 rs A E E-01 Psoriasis 6p21.33 HLA-C 6 rs C E E-01 Psoriasis 6p21.33 HLA-C

17 6 rs C E E+00 Psoriasis 6p21.33 HLA-C 6 rs C E E-01 Psoriasis 6q23.3 TNFAIP3 12 rs G E E-01 Psoriasis 12q13.2 IL23A, STAT2 13 rs A E E-01 Psoriasis 13q13.3 COG6 1 rs G E E+00 Multiple sclerosis 1p22.1 EVI5, RPL5 1 rs A E E-01 Multiple sclerosis 1p13.1 CD58 1 rs G E E-01 Multiple sclerosis 1q25.2 C1orf125 2 rs A E E-01 Multiple sclerosis 2p25.1 DDEF2 2 rs G E E-01 Multiple sclerosis 2q14.2 EN1 2 rs A E E-01 Multiple sclerosis 2q21.2 FLJ rs A E E-01 Multiple sclerosis 2q22.1 CXCR4 3 rs G E E-01 Multiple sclerosis 3q23 SLC25A36 3 rs C E E-01 Multiple sclerosis 3q24 ZIC1 3 rs G E E-01 Multiple sclerosis 3q25.32 FLJ rs G E E+00 Multiple sclerosis 4q13.2 CENPC1 4 rs G E E-01 Multiple sclerosis 4q28.3 LOC rs A E E-02 Multiple sclerosis 4q35.1 MGC rs A E E-01 Multiple sclerosis 5p13.2 IL7R 5 rs A E E+00 Multiple sclerosis 5q33.2 SGCD 6 rs G E E-01 Multiple sclerosis 6p23 JARID2 6 rs A E E-01 Multiple sclerosis 6p21.32 HLA-DRB1 6 rs G E E-01 Multiple sclerosis 6p21.32 HLA-DRB1 7 rs G E E-01 Multiple sclerosis 7p21.3 C1GALT1 7 rs A E E-01 Multiple sclerosis 7q22.1 RELN 7 rs A E E-01 Multiple sclerosis 7q31.2 MET 8 rs G E E-01 Multiple sclerosis 8p23.2 CSMD1 8 rs C E E-01 Multiple sclerosis 8q13.3 KCNB2 9 rs A E E-01 Multiple sclerosis 9p22.2 SH3GL2 9 rs G E E-01 Multiple sclerosis 9q21.13 RFK 10 rs G E E-01 Multiple sclerosis 10p15.1 IL2RA 11 rs G E E-01 Multiple sclerosis 11q14.2 RAB38 12 rs G E E-02 Multiple sclerosis 12p13.31 TNFRSF1A 12 rs A E E-01 Multiple sclerosis 12q12 PDZRN4

18 12 rs A E E-01 Multiple sclerosis 12q14.1 METTL1, CYP27B1 13 rs G E E-01 Multiple sclerosis 13q31.3 GPC5 16 rs G E E-01 Multiple sclerosis 16q22.3 C16orf47 18 rs G E E-01 Multiple sclerosis 18q21.31 WDR7 18 rs A E E-01 Multiple sclerosis 18q22.3 CBLN2 19 rs A E E+00 Multiple sclerosis 19p13.2 ACP5 19 rs A E E-01 Multiple sclerosis 19q13.42 NLRP11 20 rs G E E-01 Multiple sclerosis 20p13 C20orf46 20 rs G E E-01 Multiple sclerosis 20q13.12 CD40 6 rs A E E-01 Inflammatory bowel disease 6p21.32 HLA-DQA1 9 rs G E E+00 Inflammatory bowel disease 9q32 TNFSF15 10 rs A E E-01 Inflammatory bowel disease 10q22.3 ZMIZ1 16 rs G E E-01 Inflammatory bowel disease 16p11.2 multiple gene 19 rs A E E-01 Inflammatory bowel disease 19q13.11 Intergenic 20 rs C E E-01 Inflammatory bowel disease 20q13.33 TNFRSF6B 21 rs A E E-01 Inflammatory bowel disease 21q22.2 PSMG1 22 rs A E E-01 Inflammatory bowel disease 22q12.2 multiple gene 1 rs C E E-01 Crohn's disease 1p31.3 IL23R 1 rs NA NA 1.00E+00 Crohn's disease 1p31.3 IL23R 1 rs NA NA 1.00E+00 Crohn's disease 1p31.3 IL23R 1 rs A E E+00 Crohn's disease 1p13.2 PTPN22 1 rs A E E-01 Crohn's disease 1q23.3 ITLN1 1 rs A E E-01 Crohn's disease 1q24.3 Intergenic 2 rs G E E-01 Crohn's disease 2q37.1 ATG16L1 3 rs A E E-01 Crohn's disease 3p21.31 MST1 5 rs G E E+00 Crohn's disease 5p13.1 PTGER4 5 rs C E E+00 Crohn's disease 5p13.1 Intergenic 5 rs C E E-01 Crohn's disease 5p13.1 Intergenic 5 rs A E E+00 Crohn's disease 5q31.1 Intergenic 5 rs A E E-01 Crohn's disease 5q33.3 IL12B 6 rs A E E-01 Crohn's disease 6q27 CCR6 7 rs A E E-01 Crohn's disease 7p12.2 Intergenic 9 rs C E E-01 Crohn's disease 9p24.1 JAK2

19 10 rs A E E-01 Crohn's disease 10p15.1 NR 10 rs A E E-01 Crohn's disease 10p12.2 C10orf67 10 rs A E E-01 Crohn's disease 10q21.2 Intergenic 10 rs A E E-02 Crohn's disease 10q24.2 NKX rs G E E+00 Crohn's disease 13q14.11 Unknown 16 rs A E E+00 Crohn's disease 16q12.1 NOD2 16 rs G E E+00 Crohn's disease 16q12.1 CARD15 17 rs A E E-01 Crohn's disease 17q12 ORMDL3 17 rs G E E+00 Crohn's disease 17q21.2 STAT3 21 rs G E E-01 Crohn's disease 21q22.2 Intergenic 21 rs G E E-01 Crohn's disease 21q22.3 ICOSLG * Indicates SNPs with the most significant evidence in candidate genes previously reported. # the variant is estimated by tag SNP (r2>0.8) from HapMap CHB database. The candidate loci/variants of autoimmune diseases were available at: