Supplemental Table 1. Eighty-nine single nucleotide polymorphisms of 49 immune response genes analyzed in the study

Transcription

1 Supplemental Table 1. Eighty-nine single nucleotide polymorphisms of 49 immune response genes analyzed in the study Gene Symbol Gene ID Gene Full Name SNP ID (alphabetical order) CARD15/NOD nucleotide-binding oligomerization domain rs containing 2 CCL chemokine (C-C motif) ligand 5 rs , rs CD CD40 molecule, TNF receptor superfamily rs member 5 CD40LG 959 CD40 ligand rs CD70/TNFSF7 970 CD70 molecule rs CXCL chemokine (C-X-C motif) ligand 8 rs CXCL chemokine (C-X-C motif) ligand 14 rs CXCR chemokine (C-X-C motif) receptor 4 rs CXCR5 643 chemokine (C-X-C motif) receptor 5 rs , rs , rs FAS 355 Fas cell surface death receptor rs FCGR2A 2212 Fc fragment of IgG, low affinity IIa, receptor rs (CD32) FCN ficolin (collagen/fibrinogen domain containing rs lectin) 2 IFNG 3458 interferon, gamma rs IFNGR interferon gamma receptor 1 rs IFNGR interferon gamma receptor 2 (interferon gamma transducer 1) rs

2 IFNL interferon, lambda 3 rs , rs IFNL interferon, lambda 4 (gene/pseudogene) rs IL1B 3553 interleukin 1, beta rs , rs , rs , rs IL1RN 3557 interleukin 1 receptor antagonist rs , rs IL interleukin 4 rs , rs , rs , rs , rs , rs IL4R 3566 interleukin 4 receptor rs , rs IL interleukin 5 rs IL7R 3575 interleukin 7 receptor rs IL interleukin 10 rs , rs , rs , rs IL10RB 3588 interleukin 10 receptor, beta rs , rs IL12A 3592 interleukin 12A rs , rs , rs , rs IL12B 3593 interleukin 12B rs , rs IL12RB interleukin 12 receptor, beta 1 rs , rs IL interleukin 13 rs , rs IL interleukin 15 rs , rs , rs , rs IL15RA 3601 interleukin 15 receptor, alpha rs IL interleukin 16 rs , rs IL interleukin 18 rs , rs IL interleukin 20 rs , rs , rs IRF interferon regulatory factor 4 rs , rs ITGB integrin, beta 2 (complement component 3 rs

3 receptor 3 and 4 subunit) JAK Janus kinase 3 rs MLH mutl homolog 1 rs NCF neutrophil cytosolic factor 4, 40kDa rs , rs , rs NLRC NLR family, CARD domain containing 5 rs TGFB transforming growth factor, beta 1 rs TGFBR transforming growth factor, beta receptor II (70/80kDa) rs TLR toll-like receptor 2 rs , rs , rs TLR toll-like receptor 3 rs TLR toll-like receptor 4 rs TLR toll-like receptor 9 rs TNFRSF13C tumor necrosis factor receptor superfamily, member 13C TNFSF tumor necrosis factor (ligand) superfamily, member 10 TNFSF13B tumor necrosis factor (ligand) superfamily, Call rate < 90% (n = 5) HWE P value <0.05 (n = 7) Monomorphic (n=3) member 13b rs rs rs , rs , rs , rs , rs References

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5 10. Hoang TV, Toan NL, Song lh et al. Ficolin-2 levels and FCN2 haplotypes influence hepatitis B infection outcome in Vietnamese patients. PLoS One 2011;6:e Babel N, Vergopoulos A, Trappe RU et al. Evidence for genetic susceptibility towards development of posttransplant lymphoproliferative disorder in solid organ recipients. Transplantation 2007;84: Lan Q, Zheng T, Rothman N et al. Cytokine polymorphisms in the Th1/Th2 pathway and susceptibility to non-hodgkin lymphoma. Blood 2006;107: de NA, Takkenberg RB, Benayed R et al. Genetic variation in IL28B and treatment outcome in HBeAg-positive and -negative chronic hepatitis B patients treated with Peg interferon alfa-2a and adefovir. Scand J Gastroenterol 2012;47: Sonneveld MJ, Wong VW, Woltman AM et al. Polymorphisms near IL28B and serologic response to peginterferon in HBeAg-positive patients with chronic hepatitis B. Gastroenterology 2012;142: Migita K, Maeda Y, Abiru S et al. Polymorphisms of interleukin-1beta in Japanese patients with hepatitis B virus infection. J Hepatol 2007;46: Matsuo K, Hamajima N, Suzuki R et al. No substantial difference in genotype frequencies of interleukin and myeloperoxidase polymorphisms between malignant lymphoma patients and non-cancer controls. Haematologica 2001;86: Chen J, Liang Z, Lu F et al. Toll-like receptors and cytokines/cytokine receptors polymorphisms associate with non-response to hepatitis B vaccine. Vaccine 2011;29: Monroy CM, Cortes AC, Lopez MS et al. Hodgkin disease risk: role of genetic polymorphisms and gene-gene interactions in inflammation pathway genes. Mol Carcinog 2011;50:36-46.

6 19. Wang Y, Xu P, Zhu D et al. Association of polymorphisms of cytokine and TLR-2 genes with long-term immunity to hepatitis B in children vaccinated early in life. Vaccine 2012;30: Lan Q, Wang SS, Menashe I et al. Genetic variation in Th1/Th2 pathway genes and risk of non-hodgkin lymphoma: a pooled analysis of three population-based case-control studies. Br J Haematol 2011;153: Wang SS, Carreon JD, Hanchard B, Chanock S, Hisada M. Common genetic variants and risk for non-hodgkin lymphoma and adult T-cell lymphoma/leukemia in Jamaica. Int J Cancer 2009;125: Yucesoy B, Johnson VJ, Fluharty K et al. Influence of cytokine gene variations on immunization to childhood vaccines. Vaccine 2009;27: Truelove AL, Oleksyk TK, Shrestha S et al. Evaluation of IL10, IL19 and IL20 gene polymorphisms and chronic hepatitis B infection outcome. Int J Immunogenet 2008;35: da Silva GN, Bacchi MM, Rainho CA, de Oliveira DE. Epstein-Barr virus infection and single nucleotide polymorphisms in the promoter region of interleukin 10 gene in patients with Hodgkin lymphoma. Arch Pathol Lab Med 2007;131: Frodsham AJ, Zhang L, Dumpis U et al. Class II cytokine receptor gene cluster is a major locus for hepatitis B persistence. Proc Natl Acad Sci U S A 2006;103: Xiao H, Zhang K. Genetic polymorphisms of tumor necrosis factor-alpha and lymphotoxin-alpha in Chinese patients with non-hodgkin lymphoma. Ann Hematol 2011;90: Liu L, Xu Y, Liu Z et al. IL12 polymorphisms, HBV infection and risk of hepatocellular carcinoma in a high-risk Chinese population. Int J Cancer 2011;128:

7 28. Wu JF, Wu TC, Chen CH et al. Serum levels of interleukin-10 and interleukin-12 predict early, spontaneous hepatitis B virus e antigen seroconversion. Gastroenterology 2010;138: Lin D, Liu C, Xue M et al. The role of interleukin-15 polymorphisms in adult acute lymphoblastic leukemia. PLoS One 2010;5:e Wang SS, Cerhan JR, Hartge P et al. Common genetic variants in proinflammatory and other immunoregulatory genes and risk for non-hodgkin lymphoma. Cancer Res 2006;66: Li S, Deng Y, Chen ZP et al. Genetic polymorphism of interleukin-16 influences susceptibility to HBV-related hepatocellular carcinoma in a Chinese population. Infect Genet Evol 2011;11: Skibola CF, Bracci PM, Halperin E et al. Genetic variants at 6p21.33 are associated with susceptibility to follicular lymphoma. Nat Genet 2009;41: Wang SS, Menashe I, Cerhan JR et al. Variations in chromosomes 9 and 6p21.3 with risk of non-hodgkin lymphoma. Cancer Epidemiol Biomarkers Prev 2011;20: Chen CC, Yang SY, Liu CJ et al. Association of cytokine and DNA repair gene polymorphisms with hepatitis B-related hepatocellular carcinoma. Int J Epidemiol 2005;34: Olsson LM, Lindqvist AK, Kallberg H et al. A case-control study of rheumatoid arthritis identifies an associated single nucleotide polymorphism in the NCF4 gene, supporting a role for the NADPH-oxidase complex in autoimmunity. Arthritis Res Ther 2007;9:R Rossi D, Rasi S, Franceschetti S et al. Analysis of the host pharmacogenetic background for prediction of outcome and toxicity in diffuse large B-cell lymphoma treated with R-CHOP21. Leukemia 2009;23:

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9 Supplemental Table 2. Allele and genotype frequencies, and Hardy-Weinberg equilibrium of 89 single nucleotide polymorphisms analyzed Gene Gene ID SNP_ID Primer ID No. of typed samples (%) Genotype frequencies Allele frequencies HWE (p) - control CARD15/NOD rs C 103 C 206 Monomorphic 100% 100% CCL rs CC 47 CT 45 TT 12 C 139 T % 43% 12% 67% 33% rs CC 73 CG 26 GG 2 C 172 G % 26% 2% 85% 15% CD rs CC 27 CT 55 TT 21 C 109 T % 53% 21% 53% 47% CD40LG 959 rs GG 94 GA 4 AA 6 G 192 A 16 < % 4% 6% 92% 8% CD70/TNFSF7 970 rs TT 98 TC 6 T 202 C % 6% 97% 3% CXCL rs4073* TT 42 TA 49 T 133 A E-04 46% 54% 73% 27% CXCL rs GG 45 GC 47 CC 11 G 137 C % 46% 11% 67% 33% CXCR rs * CC 69 CT 11 TT 13 C 149 T 37 < % 12% 14% 80% 20% CXCR5 643 rs CC 80 CT 23 TT 1 C 183 T % 23% 1% 88% 12% rs GG 80 GA 24 G 184 A % 23% 88% 12% rs GG 71 GA 29 AA 4 G 171 A % 28% 4% 82% 18% FAS 355 rs TT 94 TC 9 T 197 C % 9% 96% 4% FCGR2A 2212 rs AA 52 AG 37 GG 14 A 141 G % 36% 14% 68% 32% FCN rs AA 87 AG 11 A 185 G % 11% 94% 6% IFNG 3458 rs TT 77 TA 22 AA 3 T 176 A % 22% 3% 86% 14% IFNGR rs TT 64 TC 34 CC 6 T 162 C % 33% 6% 78% 22% IFNGR rs TT 72 TC 30 CC 1 T 174 C % 29% 1% 84% 16% IFNL rs TT 95 TG 7 GG 2 T 197 G

10 91% 7% 2% 95% 5% rs AA 93 AG 9 GG 2 A 195 G % 9% 2% 94% 6% IFNL4 (IL28B) rs (65061) CC 80 CT 11 TT 4 C 171 T % 12% 4% 90% 10% IL1B 3553 rs GG 33 GA 48 AA 17 G 114 A % 49% 17% 58% 42% rs TT 33 TC 54 CC 16 T 120 C % 52% 16% 58% 42% rs AA 40 AG 47 GG 17 A 127 G % 45% 16% 61% 39% rs * AA 19 AG 31 GG 18 A 69 G % 46% 26% 51% 49% IL1RN 3557 rs AA 94 AT 9 A 197 T % 9% 96% 4% rs GG 42 GA 48 AA 14 G 132 A % 46% 13% 63% 37% IL rs TT 58 TC 41 CC 5 T 157 C % 39% 5% 75% 25% rs AA 77 AC 24 CC 3 A 178 C % 23% 3% 86% 14% rs TT 86 TG 18 T 190 G % 17% 91% 9% rs (65077) GG 83 GC 21 G 187 C % 20% 90% 10% rs CC 60 CA 39 AA 5 C 159 A % 38% 5% 76% 24% rs CC 62 CG 33 GG 4 C 157 G % 33% 4% 79% 21% IL4R 3566 rs AA 67 AG 35 GG 2 A 169 G % 34% 2% 81% 19% rs GG 37 GA 51 AA 15 G 125 A % 50% 15% 61% 39% IL rs (65093) TT 47 TC 42 CC 13 T 136 C % 41% 13% 67% 33% IL7R 3575 rs CC 28 CT 51 TT 25 C 107 T % 49% 24% 51% 49% IL rs TT 49 TG 45 GG 10 T 143 C % 43% 10% 69% 31% rs TT 49 TC 45 CC 10 T 143 C % 4% 10% 69% 31%

11 rs GG 92 GA 12 G 196 A % 12% 94% 6% rs AA 92 AG 12 A 196 G % 12% 94% 6% IL10RB 3588 rs AA 56 AG 37 GG 10 A 149 G % 36% 10% 72% 28% rs GG 36 GA 53 AA 15 G 125 A % 51% 14% 60% 40% IL12A 3592 rs AA 58 AG 33 GG 13 A 149 G % 32% 12% 72% 28% rs GG 80 GA 23 AA 1 G 183 A % 22% 1% 88% 12% rs GG 53 GA 38 AA 13 G 144 A % 37% 12% 69% 31% rs TT 79 TG 22 GG 3 T 180 G % 21% 3% 87% 13% IL12B 3593 rs GG 35 GC 48 CC 21 G 118 C % 46% 20% 57% 43% rs AA 36 AC 48 CC 20 A 120 C % 46% 19% 58% 42% IL12RB rs TT 46 TC 46 CC 12 T 138 C % 44% 12% 66% 34% rs * CC 42 CG 14 C 98 G % 25% 88% 12% IL rs GG 47 GA 46 AA 11 G 140 A % 44% 11% 67% 33% rs CC 67 CT 26 TT 1 C 160 T % 28% 1% 85% 15% IL rs AA 40 AC 45 CC 19 A 125 C % 43% 18% 60% 40% rs CC 40 CA 45 AA 19 C 125 A % 43% 18% 60% 40% rs TT 37 TC 48 CC 19 T 122 C % 46% 18% 59% 41% rs AA 39 AG 44 GG 21 A 122 G % 42% 20% 59% 41% IL15RA 3601 rs AA 27 AC 59 CC 18 A 113 C % 57% 17% 54% 46% IL rs GG 67 GA 34 AA 3 G 168 A % 33% 3% 81% 19% rs TT 74 TG 29 GG 1 T 177 G

12 71% 28% 1% 85% 155 IL rs187238* NA NA NA NA NA NA NA NA NA NA NA rs TT 74 TC 25 CC 3 T 173 C % 25% 3% 85% 15% IL rs CC 77 CT 22 TT 2 C 176 T % 22% 2% 87% 13% rs CC 63 CT 38 TT 3 C 164 T % 37% 3% 79% 21% rs GG 41 GC 47 CC 16 G 129 C % 45% 15% 62% 38% IRF rs AA 53 AG 41 GG 10 A 147 G % 39% 10% 71% 29% rs GG 85 GC 19 G 189 C % 18% 91% 9% ITGB rs TT 31 TC 50 CC 23 T 112 C % 48% 22% 54% 46% JAK rs CC 33 CT 48 TT 23 C 114 T % 46% 22% 55% 455% MLH rs AA 30 AG 57 GG 16 A 117 G % 55% 16% 57% 43% NCF rs CC 34 CT 57 TT 13 C 125 T % 55% 12% 60% 40% rs AA 50 AG 48 GG 6 A 148 G % 46% 6% 71% 29% rs TT 82 TC 21 CC 1 T 185 C % 20% 1% 89% 11% NLRC rs GG 103 G 206 Monomorphic 100% 100% TGFB rs TT 31 TC 54 CC 19 T 116 C % 52% 18% 56% 44% TGFBR rs CC 52 CT 40 TT 8 C 144 T % 40% 9% 72% 28% TLR rs TT 55 TC 41 CC 8 T 151 C % 40% 8% 73% 27% rs GG 104 G 208 Monomorphic 100% 100% rs GG 24 GT 55 TT 23 G 103 T % 54% 23% 50% 50% TLR rs (65065) CC 54 CA 45 AA 5 C 153 A % 43% 5% 74% 26%

13 TLR rs TT 73 TC 30 CC 16 T 176 C % 29% 1% 85% 15% TLR rs TT 44 TC 43 CC 14 T 131 C % 43% 14% 65% 35% TNFRSF13C rs GG 95 GA 8 G 198 A % 8% 96% 4% TNFSF rs CC 90 CA 11 C 191 A % 11% 95% 5% TNFSF13B rs GG 64 GA 36 AA 2 G 164 A % 35% 2% 80% 20% rs TT 103 GG 1 T 206 G % 1% 99% 1% rs CC 40 CT 45 TT 19 C 125 T % 43% 18% 60% 40% rs AA 33 AC 49 CC 22 A 115 C % 47% 21% 55% 45% rs TT 32 TA 48 AA 23 T 112 A % 47% 22% 54% 46% *Call rate < 90% (n = 5) HWE < 0.05 (n = 7) Monomorphic (n = 3) HWE, Hardy-Weinberg equilibrium

14 Supplemental Table 3. The association of 74 single nucleotide polymorphisms with the development of HBsAg reverse seroconversion Gene SNP_ID Model Genotype HBV-RS, no HBV-RS, yes OR (95% CI) P value AIC BIC CCL5 rs Recessive C/C-C/T 78 (86.7%) 14 (100%) T/T 12 (13.3%) 0 (0%) 0.00 (0.00-NA) rs Dominant C/C 64 (72.7%) 9 (69.2%) G/C-G/G 24 (27.3%) 4 (30.8%) 1.19 ( ) CD40 rs Dominant C/C 26 (29.2%) 1 (7.1%) C/T-T/T 63 (70.8%) 13 (92.9%) 5.37 ( Recessive C/C-C/T 71 (79.8%) 11 (78.6%) T/T 18 (20.2%) 3 (21.4%) 1.08 ( ) CD70/TNFSF7 rs T/T 85 (94.4%) 13 (92.9%) C/T 5 (5.6%) 1 (7.1%) 1.31 ( ) CXCL14 rs Dominant G/G 37 (41.6%) 8 (57.1%) C/G-C/C 52 (58.4%) 6 (42.9%) 0.53 ( ) CXCR5 rs Recessive C/C-C/T 89 (98.9%) 14 (100%) T/T 1 (1.1%) 0 (0%) 0.00 (0.00-NA) rs G/G 67 (74.4%) 13 (92.9%) A/G 23 (25.6%) 1 (7.1%) 0.22 ( ) rs Dominant G/G 60 (66.7%) 11 (78.6%) A/G-A/A 30 (33.3%) 3 (21.4%) 0.55 ( ) FAS rs T/T 81 (91%) 13 (92.9%) C/T 8 (9%) 1 (7.1%) 0.78 ( ) FCN2 rs A/A 76 (90.5%) 11 (78.6%) A/G 8 (9.5%) 3 (21.4%) 2.59 ( ) IFNG rs Dominant T/T 69 (78.4%) 8 (57.1%) A/T-A/A 19 (21.6%) 6 (42.9%) 2.72 ( ) IFNGR1 rs Recessive T/T-C/T 86 (95.6%) 12 (85.7%) C/C 4 (4.4%) 2 (14.3%) 3.58 ( ) IFNGR2 rs Dominant T/T 63 (70.8%) 9 (64.3%) C/T-C/C 26 (29.2%) 5 (35.7%) 1.35 ( ) IL1B rs16944 Dominant G/G 30 (34.9%) 3 (25%) A/G-A/A 56 (65.1%) 9 (75%) 1.61 ( ) rs Dominant T/T 30 (33.7%) 3 (21.4%)

15 C/T-C/C 59 (66.3%) 11 (78.6%) 1.86 ( ) rs Recessive A/A-A/G 76 (84.4%) 11 (78.6%) G/G 14 (15.6%) 3 (21.4%) 1.48 ( ) IL1RN rs A/A 82 (92.1%) 12 (85.7%) A/T 7 (7.9%) 2 (14.3%) 1.95 ( ) rs Dominant G/G 34 (37.8%) 8 (57.1%) A/G-A/A 56 (62.2%) 6 (42.9%) 0.46 ( ) IL4 rs Recessive T/T-C/T 86 (95.6%) 13 (92.9%) C/C 4 (4.4%) 1 (7.1%) 1.65 ( rs Dominant A/A 69 (76.7%) 8 (57.1%) A/C-C/C 21 (23.3%) 6 (42.9%) 2.46 ( ) rs T/T 72 (80%) 14 (100%) T/G 18 (20%) 0 (0%) 0.00 (0.00-NA) rs G/G 69 (76.7%) 14 (100%) C/G 21 (23.3%) 0 (0%) 0.00 (0.00-NA) rs Recessive C/C-A/C 86 (95.6%) 13 (92.9%) A/A 4 (4.4%) 1 (7.1%) 1.65 ( ) rs Recessive C/C-C/G 82 (96.5%) 13 (92.9%) G/G 3 (3.5%) 1 (7.1%) 2.10 ( ) IL4R rs Dominant A/A 60 (66.7%) 7 (50%) A/G-G/G 30 (33.3%) 7 (50%) 2.00 ( ) rs Dominant G/G 33 (37.1%) 4 (28.6%) A/G-A/A 56 (62.9%) 10 (71.4%) 1.47 ( ) IL5 rs Dominant T/T 43 (48.3%) 4 (30.8%) C/T-C/C 46 (51.7%) 9 (69.2%) 2.10 ( ) IL7R rs Recessive C/C-C/T 67 (74.4%) 12 (85.7%) T/T 23 (25.6%) 2 (14.3%) 0.49 ( ) IL10 rs Dominant T/T 45 (50%) 4 (28.6%) T/G-G/G 45 (50%) 10 (71.4%) 2.50 ( ) rs Dominant T/T 45 (50%) 4 (28.6%) C/T-C/C 45 (50%) 10 (71.4%) 2.50 ( ) rs G/G 80 (88.9%) 12 (85.7%) A/G 10 (11.1%) 2 (14.3%) 1.33 ( ) rs A/A 80 (88.9%) 12 (85.7%)

16 A/G 10 (11.1%) 2 (14.3%) 1.33 ( ) IL10RB rs Dominant A/A 47 (52.8%) 9 (64.3%) A/G-G/G 42 (47.2%) 5 (35.7%) 0.62 ( ) rs Recessive G/G-A/G 79 (87.8%) 10 (71.4%) A/A 11 (12.2%) 4 (28.6%) 2.87 ( ) IL12A rs Dominant G/G 69 (76.7%) 11 (78.6%) A/G-A/A 21 (23.3%) 3 (21.4%) 0.90 ( ) rs Dominant G/G 44 (48.9%) 9 (64.3%) A/G-A/A 46 (51.1%) 5 (35.7%) 0.53 ( ) rs Recessive T/T-T/G 88 (97.8%) 13 (92.9%) G/G 2 (2.2%) 1 (7.1%) 3.38 ( ) IL12B rs Dominant G/G 28 (31.1%) 7 (50%) C/G-C/C 62 (68.9%) 7 (50%) 0.45 ( ) rs Dominant A/A 29 (32.2%) 7 (50%) A/C-C/C 61 (67.8%) 7 (50%) 0.48 ( ) IL12RB1 rs Dominant T/T 39 (43.3%) 7 (85.7%) C/T-C/C 51 (56.7%) 7 (14.3%) 0.76 ( ) IL13 rs Dominant G/G 40 (44.4%) 7 (50%) A/G-A/A 50 (55.6%) 7 (50%) 0.80 ( ) Recessive G/G-A/G 83 (92.2%) 10 (71.4%) A/A 7 (7.8%) 4 (28.6%) 4.74 ( ) rs Dominant C/C 59 (73.8%) 8 (57.1%) C/T-T/T 21 (26.2%) 6 (42.9%) 2.11 ( ) IL15 rs Dominant A/A 36 (40%) 4 (28.6%) A/C-C/C 54 (60%) 10 (71.4%) 1.67 ( ) rs Dominant C/C 36 (40%) 4 (28.6%) A/C-A/A 54 (60%) 10 (71.4%) 1.67 ( ) rs Dominant T/T 34 (37.8%) 3 (21.4%) C/T-C/C 56 (62.2%) 11 (78.6%) 2.23 ( ) rs Recessive A/A-A/G 73 (81.1%) 10 (71.4%) G/G 17 (18.9%) 4 (28.6%) 1.72 ( ) IL15RA rs Dominant A/A 24 (26.7%) 3 (21.4%) A/C-C/C 66 (73.3%) 11 (78.6%) 1.33 ( ) IL16 rs Dominant G/G 60 (66.7%) 7 (50%)

17 A/G-A/A 30 (33.3%) 7 (50%) 2.00 ( ) rs Dominant T/T 65 (72.2%) 9 (64.3%) T/G-G/G 25 (27.8%) 5 (35.7%) 1.44 ( ) IL18 rs CodominanT/T 67 (76.1%) 7 (50%) C/T 18 (20.4%) 7 (50%) 3.72 ( ) C/C 3 (3.4%) 0 (0%) 0.00 (0.00-NA) Dominant T/T 67 (76.1%) 7 (50%) C/T-C/C 21 (23.9%) 7 (50%) 3.19 ( ) Recessive T/T-C/T 85 (96.6%) 14 (100%) C/C 3 (3.4%) 0 (0%) 0.00 (0.00-NA) IL20 rs Recessive C/C-C/T 85 (97.7%) 14 (78.6%) T/T 2 (2.3%) 0 (21.4%) 0.00 (0.00-NA) rs CodominanC/C 58 (64.4%) 5 (35.7%) C/T 29 (32.2%) 9 (64.3%) 3.60 ( ) T/T 3 (3.3%) 0 (0%) 0.00 (0.00-NA) Dominant C/C 58 (64.4%) 5 (35.7%) C/T-T/T 32 (35.6%) 9 (64.3%) 3.26 ( ) Recessive C/C-C/T 87 (96.7%) 14 (100%) T/T 3 (3.3%) 0 (0%) 0.00 (0.00-NA) rs Dominant G/G 34 (37.8%) 7 (50%) C/G-C/C 56 (62.2%) 7 (50%) 0.61 ( ) IRF4 rs Recessive A/A-A/G 80 (88.9%) 14 (100%) G/G 10 (11.2%) 0 (0%) 0.00 (0.00-NA) rs G/G 74 (82.2%) 11 (78.6%) C/G 16 (17.8%) 3 (21.4%) 1.26 ( ) ITGB2 rs Dominant T/T 28 (31.1%) 3 (21.4%) C/T-C/C 62 (68.9%) 62 (68.9%) 1.66 ( ) JAK3 rs3008 Recessive C/C-C/T 72 (80%) 9 (64.3%) T/T 18 (20%) 5 (35.7%) 2.22 ( ) MLH1 rs Recessive A/A-A/G 76 (85.4%) 11 (78.6%) G/G 13 (14.6%) 3 (21.4%) 1.59 ( ) NCF4 rs Recessive C/C-C/T 80 (88.9%) 11 (78.6%) T/T 10 (11.1%) 3 (21.4%) 2.18 ( ) rs Dominant A/A 46 (51.1%) 4 (28.6%)

18 A/G-G/G 44 (48.9%) 10 (71.4%) 2.61 ( ) rs Dominant T/T 72 (79.8%) 10 (71.4%) C/T-C/C 18 (20.2%) 4 (28.6%) 1.60 ( ) TGFB1 rs Dominant T/T 24 (26.7%) 7 (50%) C/T-C/C 66 (73.3%) 7 (50%) 0.36 ( ) Recessive T/T-C/T 72 (80%) 13 (92.9%) C/C 18 (20%) 1 (7.1%) 0.31 ( ) TGFBR2 rs Dominant C/C 46 (52.9%) 6 (41.7%) C/T-T/T 41 (47.1%) 7 (58.3%) 1.31 ( ) TLR2 rs Recessive T/T-C/T 82 (91.1%) 14 (100%) C/C 8 (9%) 0 (0%) 0.00 (0.00-NA) rs Recessive G/G-T/G 67 (76.1%) 12 (85.7%) T/T 21 (23.9%) 2 (14.3%) 0.53 ( ) TLR3 rs Recessive C/C-A/C 85 (94.4%) 14 (100%) A/A 5 (5.6%) 0 (0%) 0.00 (0.00-NA) TLR4 rs Dominant T/T 62 (68.9%) 11 (78.6%) C/T-C/C 28 (31.1%) 3 (21.4%) 0.60 ( ) TLR9 rs Dominant T/T 39 (44.8%) 5 (35.7%) C/T-C/C 48 (55.2%) 9 (64.3%) 1.46 ( ) TNFRSF13C rs G/G 84 (94.4%) 11 (78.6%) A/G 5 (5.6%) 3 (21.4%) 4.58 ( ) TNFSF10 rs C/C 77 (88.5%) 13 (92.9%) A/C 10 (11.5%) 1 (7.1%) 0.59 ( ) TNFSF13B rs Recessive G/G-A/G 87 (98.9%) 13 (92.9%) A/A 1 (1.5%) 1 (7.1%) 6.69 ( ) rs Recessive C/C-C/T 73 (81.1%) 12 (85.7%) T/T 17 (18.9%) 2 (14.3%) 0.72 ( ) rs CodominanA/A 32 (35.6%) 1 (7.1%) (42.2%) 11 (78.6%) 9.26 ( ) 20 (22.2%) 2 (14.3%) 3.20 ( ) Dominant A/A 32 (35.6%) 1 (7.1%) A/C-C/C 32 (35.6%) 13 (92.9%) 7.17 ( ) Recessive A/C-A/C 70 (77.8%) 12 (85.7%) C/C 20 (22.2%) 2 (14.3%) 0.58 ( )

19 rs CodominanT/T 31 (34.8%) 1 (7.1%) A/T 37 (41.6%) 11 (78.6%) 9.22 ( ) A/A 21 (23.6%) 2 (14.3%) 2.95 ( ) Dominant T/T 31 (34.8%) 1 (7.1%) A/T-A/A 58 (65.2%) 13 (92.9%) 6.95 ( ) Recessive T/T-A/T 68 (76.4%) 12 (85.7%) A/A 21 (23.6%) 2 (14.3%) 0.54 ( )

20 Supplemental Table 4. Linkage disequilibrium analysis of nine candidate single nucleotide polymorphisms D statistic CCL5 IL13 IL18 IL20 CD40 TNFSF13B IL4 TNFSF13B IL4 rs rs rs rs rs rs rs rs rs CCL5 rs IL13 rs IL18 rs IL20 rs CD40 rs TNFSF13B rs IL4 rs TNFSF13B rs IL4 rs D' statistic CCL5 IL13 IL18 IL20 CD40 TNFSF13B IL4 TNFSF13B IL4 rs rs rs rs rs rs rs rs rs CCL5 rs IL13 rs IL18 rs IL20 rs CD40 rs TNFSF13B rs IL4 rs TNFSF13B rs IL4 rs r statistic CCL5 IL13 IL18 IL20 CD40 TNFSF13B IL4 TNFSF13B IL4 rs rs rs rs rs rs rs rs rs CCL5 rs IL13 rs IL18 rs IL20 rs CD40 rs TNFSF13B rs IL4 rs TNFSF13B rs IL4 rs

21 P-values CCL5 IL13 IL18 IL20 CD40 TNFSF13B IL4 TNFSF13B IL4 rs rs rs rs rs rs rs rs rs CCL5 rs IL13 rs IL18 rs IL20 rs CD40 rs TNFSF13B rs IL4 rs TNFSF13B rs IL4 rs

22 Supplemental Table 5. Genotype distribution within haplotypes of IL4 rs ~rs and TNFSF13B rs ~rs IL4 rs n (%) P G/G C/G < rs n (%) T/T 83 (79.8) 3 (2.9) T/G 0 (0) 18 (17.3) TNFSF13B rs n (%) P T/T A/T-A/A < rs n (%) A/A 32 (31.1) 1 (1) A/C-C/C 0 (0) 70 (68) 1 Fisher's Exact Test n, number of patients; %, percent of total patients analyzed