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A genome-wide association study identifies two new cervical cancer susceptibility loci at 4q12 and 17q12 Supplementary Materials Yongyong Shi 1-4,42, Li Li 5,42, Zhibin Hu 6,7,42, Shuang Li 1,42, Shixuan Wang 1,42, Jihong Liu 8,42, Chen Wu 9,42, Lin He 2-4, Jianfeng Zhou 10, Zhiqiang Li 2-4, Ting Hu 1, Yile Chen 11, Yao Jia 1, Shaoshuai Wang 1, Li Wu 11, Xiaodong Cheng 12, Zhijun Yang 5, Ru Yang 1, Xiong Li 1, Kecheng Huang 1, Qinghua Zhang 1, Hang Zhou 1, Fangxu Tang 1, Zhilan Chen 1, Jian Shen 1, Jie Jiang 6,7, Hu Ding 10, Hui Xing 13, Shulan Zhang 14, Pengpeng Qu 15, Xiaojie Song 16, Zhongqiu Lin 17, Dongrui Deng 1, Ling Xi 1, Weiguo Lv 12, Xiaobing Han 18, Guangshi Tao 19, Lixing Yan 20, Zhedong Han 20, Zhuang Li 5, Xiaoping Miao 21, Shandong Pan 6,7, Yuanming Shen 12, Hui Wang 1, Dan Liu 1, Ee Gong 1, Zheng Li 8, Limei Zhou 15, Xiaomei Luan 14, Chuping Wang 22, Qian Song 23, Sufang Wu 24, Hongbin Xu 25, Jiawei Shen 2-4, Fulin Qiang 26, Gang Ma 27, Li Liu 26, Xiaojun Chen 26, Jibin Liu 26, Jiangping Wu 28, Yan Shen 28, Yang Wen 6,7, Minjie Chu 6,7, Jiang Yu 29, Xiaoxia Hu 30, Yujuan Fan 31, Hongying He 32, Yanming Jiang 33, Zhiying Lei 34, Cui Liu 35, Jianhua Chen 2, 36, Yuan Zhang 37, Cunjian Yi 38, Shuangyun Chen 39, Wenjin Li 2, Daowen Wang 10, Zehua Wang 37, Wen Di 40, Keng Shen 41, Dongxin Lin 9, Hongbing Shen 6,7, Youji Feng 24, Xing Xie 12, Ding Ma 1 1

Index Supplementary Figure 1. The principal components analysis (PCA) of all initial GWAS samples (1,364 cases and 3,028 controls) and HapMap 270 individuals (JPT+CHB, CEU and YRI) implemented in the software package EIGENSTRAT. Supplementary Figure 2. Plots of the first two components derived from a principle component analysis implemented in the software package EIGENSTRAT. Supplementary Figure 3. Quantile-Quantile plots of observed P values in log 10 scale. Supplementary Figure 4. Scatter plot of P values in log 10 scale in the Initial discovery set. Supplementary Figure 5. Regional plot of the four identified marker SNPs, including rs13117307 at 4q12 (a), rs8067378 at 17q12 (b), rs4282438 and rs9277952 at 6p21.32 (c-d). Results ( log 10 P) are shown for SNPs in the region flanking 150 kb on either side of the marker SNPs in the Initial discovery set. Supplementary Table 1. Associations results of 22 SNPs in the first stage of GWAS. Supplementary Table 2. Associations results of 22 SNPs in the Follow-up 1. Supplementary Table 3. Associations results of 13 SNPs in the Follow-up 2. Supplementary Table 4. Association results of 13 SNPs in the Matched discovery study, case-control validation and the combined samples. 2

Supplementary Table 5. Association results of 13 SNPs in the Stringent-matched discovery study and the combined samples. Supplementary Table 6. Summary results of four SNPs in the GWAS, case-control validation and the combined samples. Supplementary Table 7. Stepwise logistic regression analysis for independent association in GWAS. Supplementary Table 9. Pair-wise LD between HLA-DP alleles tagging SNPs and two representative SNPs (rs4282438 and rs9277952). Supplementary Table 10. Gene expression analysis of the candidate genes between cervical cancer cases and controls from 2 available datasets. Supplementary Table 11. Expression quantitative trait loci (eqtl) analysis of rs13117307, rs8067378and rs9277952 for lymphoblastic cell lines of HAPMAP samples. Supplementary Table 12. Association results of 11 positive SNPs in CIN samples. Supplementary Table 14. Oligonucleotides used for HLA-DPA1 and HLA-DPB1 sequencing. 3

Supplementary Figure 1. The principal components analysis (PCA) of all initial GWAS samples (1,364 cases and 3,028 controls) and HapMap 270 individuals (JPT+CHB, CEU and YRI) implemented in the software package EIGENSTRAT. Plots of the first two PCs from the PCA of 4,392 samples and 270 HapMap individuals were shown with different colors. 4

Supplementary Figure 2. Plots of the first two components derived from a principle component analysis implemented in the software package EIGENSTRAT. (a) the Initial discovery set; (b) the Stringent-matched discovery set. (c) the Matched discovery set; 5

Supplementary Figure 3. Quantile-Quantile plots of observed P values in log 10 scale. (a) the Initial discovery set; (b) the Matched discovery set; (c) the Stringent-matched discovery set. 6

Supplementary Figure 4. Scatter plot of P values in log 10 scale in the Initial discovery set. 7

Supplementary Figure 5. Regional plot of the four identified marker SNPs, including rs13117307 at 4q12 (a), rs8067378 at 17q12 (b), rs4282438 and rs9277952 at 6p21.32 (c-d). Results ( log 10 P) are shown for SNPs in the region flanking 150 kb on either side of the marker SNPs (in purple). The genes within the region of interest are shown as arrows. Association results of both genotyped (circles) and imputed (crotch-shaped) SNPs in the Initial discovery set. 8

Chr SNP Position Associated Gene Supplementary Table 1. Associations results of 22 SNPs in the first stage of GWAS. a MA Initial discovery study (1,364 cases vs. 3,028 controls) b MAF c P value OR (95% CI) a MA Matched discovery study (1,305cases vs. 1,444 controls) b MAF d P value OR (95% CI) 1p21.1 rs12044588 105863397 Intergenic C 0.33/0.28 1.59E-05 1.26 (1.14-1.41) C 0.33/0.28 3.41E-05 1.28 (1.14-1.44) 4p15.32 rs16892888 15662277 PROM1 A 0.15/0.18 1.02E-07 0.69 (0.60-0.79) A 0.15/0.20 7.03E-07 0.69 (0.60-0.80) 4q12 rs13117307 56446497 EXOC1 T 0.14/0.11 2.59E-05 1.38 (1.19-1.60) T 0.14/0.10 4.00E-05 1.42 (1.20-1.68) 4q12 rs1447045 56456305 EXOC1 G 0.14/0.12 2.36E-05 1.38 (1.19-1.59) G 0.14/0.10 3.71E-05 1.42 (1.20-1.68) 4q34.3 rs7698554 180290498 Intergenic C 0.50/0.45 1.39E-05 1.25 (1.13-1.38) C 0.51/0.45 2.23E-05 1.26 (1.13-1.41) 6p21.32 rs2116260 33133418 HLA-DPA1 C 0.49/0.49 1.00E-05 0.80 (0.72-0.88) T 0.51/0.45 1.45E-05 1.27 (1.14-1.42) 6p21.32 rs4282438 33180150 HLA-DPB1 G 0.34/0.37 2.66E-08 0.74 (0.67-0.82) G 0.35/0.42 3.10E-08 0.73 (0.65-0.81) 6p21.32 rs3117039 33193829 HLA-DPB2 A 0.41/0.39 1.96E-05 1.25 (1.13-1.39) A 0.41/0.38 2.45E-05 1.27 (1.14-1.42) 6p21.32 rs4713607 33198814 HLA-DPB2 A 0.51/0.49 4.31E-05 1.24 (1.12-1.37) A 0.50/0.45 6.64E-05 1.25 (1.12-1.39) 6p21.32 rs3129275 33202236 HLA-DPB2 G 0.46/0.51 1.53E-06 0.78 (0.71-0.86) A 0.54/0.47 6.78E-07 1.32 (1.18-1.47) 6p21.32 rs3117008 33204252 HLA-DPB2 C 0.44/0.48 3.03E-06 0.79 (0.71-0.87) C 0.45/0.51 5.14E-06 0.78 (0.70-0.87) 6p21.32 rs9391756 33223772 COL11A2 A 0.42/0.44 2.36E-07 0.76 (0.69-0.85) A 0.42/0.49 3.68E-07 0.75 (0.68-0.84) 6p21.32 rs213210 33283802 Mir-219-1 C 0.47/0.49 1.72E-05 0.80 (0.72-0.89) T 0.53/0.46 3.17E-06 1.30 (1.16-1.45) 6p21.32 rs9277952 33312252 Intergenic A 0.39/0.43 2.45E-06 0.78 (0.70-0.86) A 0.40/0.46 9.70E-06 0.78 (0.70-0.87) 8q23.3 rs2694037 116863407 Intergenic C 0.42/0.38 1.83E-06 1.29 (1.16-1.43) C 0.41/0.35 3.64E-06 1.31 (1.17-1.46) 8q23.3 rs2694042 116895441 Intergenic G 0.40/0.36 1.35E-05 1.26 (1.13-1.39) G 0.39/0.34 2.91E-05 1.27 (1.14-1.42) 9q22.32 rs7039582 96361756 FBP2 T 0.20/0.23 6.69E-06 0.75 (0.66-0.85) T 0.20/0.25 3.58E-05 0.75 (0.66-0.86) 10p11.23 rs10826702 30135992 Intergenic C 0.25/0.21 8.00E-05 1.27 (1.13-1.43) C 0.25/0.21 5.49E-05 1.31 (1.15-1.49) 10q21.3 rs10762170 68923895 CTNNA3 A 0.33/0.37 5.74E-06 0.78 (0.70-0.87) A 0.33/0.38 7.35E-05 0.79 (0.71-0.89) 14q21.3 rs2295158 44449239 C14orf28 A 0.13/0.11 3.82E-05 1.38 (1.18-1.61) A 0.13/0.10 5.36E-05 1.43 (1.20-1.70) 17q12 rs12948097 32275889 Intergenic A 0.29/0.34 3.48E-06 0.77 (0.69-0.86) A 0.29/0.35 2.65E-05 0.78 (0.69-0.88) 17q12 rs8067378 35304874 GSDMB G 0.29/0.27 1.59E-06 1.32 (1.18-1.48) G 0.29/0.25 5.09E-05 1.29 (1.14-1.46) a MA: Minor allele; b MAF: Minor allele-frequency; c P value: PCA-adjusted P value for the samples in the Initial discovery study; d P value: PCA-adjusted P value for the samples in the Matched discovery study; OR: odds ratio for minor allele; 95% CI: 95% confidence intervals. 9

Chr Supplementary Table 2. Associations results of 22 SNPs in the Follow-up 1. SNP Meta-analysis of Follow-up 1 North Center South (1,824 cases vs. 3,808 controls) (600 cases vs. 1,617 controls) (460 cases vs. 968 controls) (764 cases vs. 1,223 controls) a MA P value 1 rs12044588 C 2.02E-01 4 rs16892888 A 1.72E-01 4 rs13117307 T 1.47E-04 4 rs1447045 G 2.11E-03 4 rs7698554 C 1.99E-01 6 rs2116260 T 3.50E-07 6 rs4282438 G 4.29E-11 6 rs3117039 A 2.03E-04 6 rs4713607 A 1.24E-06 6 rs3129275 A 4.83E-04 6 rs3117008 C 1.11E-08 OR OR OR OR a MA F_A P value a MA F_A P value a MA F_A P value (95% CI) (95% CI) (95% CI) (95% CI) 0.94 (0.86-1.03) 0.93 (0.84-1.03) 1.29 (1.13-1.47) 1.22 (1.07-1.38) 1.05 (0.97-1.14) 1.23 (1.13-1.33) 0.75 (0.69-0.82) 1.17 (1.08-1.27) 1.23 (1.13-1.33) 1.15 (1.07-1.25) 0.79 (0.72-0.85) C 0.26 3.17E-01 A 0.17 2.86E-01 T 0.13 3.13E-03 G 0.14 2.29E-02 C 0.47 5.69E-01 C 0.43 2.86E-06 G 0.29 4.38E-06 A 0.43 2.65E-02 A 0.53 1.43E-03 G 0.48 2.62E-01 C 0.43 4.07E-03 0.93 (0.80-1.08) 0.91 (0.76-1.08) 1.36 (1.11-1.67) 1.25 (1.03-1.52) 1.04 (0.91-1.19) 0.73 (0.64-0.83) 0.71 (0.61-0.82) 1.17 (1.02-1.35) 1.25 (1.09-1.44) 0.93 (0.81-1.06) 0.82 (0.71-0.94) C 0.3 9.65E-01 A 0.19 8.85E-01 T 0.14 6.48E-02 G 0.13 1.32E-01 C 0.47 5.28E-01 T 0.43 1.93E-01 G 0.35 4.13E-05 A 0.43 2.16E-03 A 0.51 2.39E-04 A 0.56 9.43E-06 C 0.42 1.39E-05 1.00 (0.84-1.18) 0.99 (0.81-1.21) 1.25 (0.99-1.58) 1.20 (0.95-1.51) 1.05 (0.90-1.23) 1.11 (0.95-1.30) 0.71 (0.60-0.83) 1.29 (1.10-1.53) 1.35 (1.15-1.59) 1.43 (1.22-1.68) 0.70 (0.59-0.82) C 0.29 2.83E-01 A 0.22 2.91E-01 T 0.09 9.51E-02 G 0.09 1.45E-01 C 0.45 3.16E-01 T 0.42 8.86E-03 G 0.36 4.31E-03 A 0.43 1.79E-01 A 0.49 8.58E-02 G 0.46 3.60E-01 C 0.42 3.99E-03 0.92 (0.80-1.07) 0.92 (0.79-1.08) 1.23 (0.97-1.56) 1.19 (0.94-1.50) 1.07 (0.94-1.22) 1.19 (1.04-1.35) 0.82 (0.71-0.94) 1.10 (0.96-1.26) 1.12 (0.98-1.28) 0.94 (0.83-1.07) 0.82 (0.72-0.94) 10

6 rs9391756 A 1.25E-09 0.77 (0.71-0.84) A 0.37 4.40E-06 0.72 (0.63-0.83) A 0.41 8.99E-05 0.72 (0.61-0.85) A 0.41 2.99E-02 0.86 (0.76-0.99) 6 rs213210 T 3.09E-08 1.26 (1.16-1.37) C 0.41 3.34E-05 0.75 (0.66-0.86) T 0.52 1.89E-02 1.21 (1.03-1.42) C 0.43 2.79E-03 0.82 (0.72-0.93) 6 rs9277952 A 4.60E-02 0.92 (0.85-1.00) A 0.37 6.85E-02 0.88 (0.77-1.01) A 0.42 9.32E-02 0.87 (0.74-1.02) A 0.35 9.55E-01 1.00 (0.87-1.14) 8 rs2694037 C 2.38E-01 1.05 (0.97-1.14) C 0.41 4.29E-01 1.06 (0.92-1.21) C 0.41 8.15E-01 1.02 (0.87-1.20) C 0.37 3.49E-01 1.07 (0.93-1.22) 8 rs2694042 G 9.43E-02 1.07 (0.99-1.17) G 0.39 2.29E-01 1.09 (0.95-1.25) G 0.4 3.30E-01 1.09 (0.92-1.28) G 0.34 4.62E-01 1.05 (0.92-1.21) 9 rs7039582 T 6.69E-02 0.91 (0.83-1.00) T 0.2 3.87E-02 0.84 (0.71-0.99) T 0.23 8.91E-01 1.01 (0.84-1.22) T 0.25 2.58E-01 0.92 (0.79-1.07) 10 rs10826702 C 7.40E-01 0.98 (0.89-1.09) C 0.2 3.91E-01 0.93 (0.79-1.10) C 0.22 6.94E-01 1.04 (0.86-1.26) C 0.17 9.82E-01 1.00 (0.84-1.19) 10 rs10762170 A 9.97E-01 1.00 (0.92-1.09) A 0.34 1.98E-01 0.91 (0.79-1.05) A 0.38 2.78E-01 1.09 (0.93-1.28) A 0.34 7.16E-01 1.03 (0.89-1.18) 14 rs2295158 A 2.41E-02 1.16 (1.02-1.32) A 0.13 7.40E-02 1.20 (0.98-1.48) A 0.13 1.05E-01 1.22 (0.96-1.55) A 0.09 6.38E-01 1.06 (0.84-1.33) 17 rs12948097 A 8.03E-01 1.01 (0.93-1.10) A 0.3 9.20E-02 0.88 (0.76-1.02) A 0.33 2.76E-01 1.10 (0.93-1.30) A 0.34 2.69E-01 1.08 (0.94-1.24) 17 rs8067378 G 4.36E-03 1.14 (1.04-1.25) G 0.32 4.67E-02 1.16 (1.00-1.34) G 0.28 3.43E-02 1.22 (1.02-1.46) G 0.28 3.43E-01 1.07 (0.93-1.24) a MA: Minor allele; OR: odds ratio for minor allele; 95% CI: 95% confidence intervals. 11

Supplementary Table 3. Associations results of 13 SNPs in the Follow-up 2. Chr SNP BP A1 F_A F_U A2 P value OR 95% CI 4 rs13117307 56446497 T 0.13 0.11 C 1.03E-03 1.21 1.08-1.36 4 rs1447045 56456305 G 0.12 0.11 A 9.69E-03 1.17 1.04-1.31 6 rs2116260 33133418 T 0.48 0.44 C 1.08E-06 1.21 1.12-1.30 6 rs4282438 33180150 G 0.35 0.41 T 1.40E-10 0.77 0.71-0.84 6 rs3117039 33193829 A 0.41 0.37 G 6.44E-06 1.20 1.11-1.29 6 rs4713607 33198814 A 0.51 0.46 G 8.64E-08 1.23 1.14-1.33 6 rs3129275 33202236 G 0.47 0.52 A 1.36E-09 0.79 0.73-0.85 6 rs3117008 33204252 C 0.44 0.51 T 5.68E-11 0.77 0.72-0.83 6 rs9391756 33223772 A 0.43 0.48 C 3.62E-09 0.79 0.73-0.86 6 rs213210 33283802 T 0.50 0.47 C 7.31E-05 1.17 1.08-1.26 6 rs9277952 33312252 A 0.41 0.46 G 1.98E-06 0.83 0.77-0.90 14 rs2295158 44449239 A 0.12 0.11 G 7.19E-01 1.02 0.91-1.15 17 rs8067378 35304874 G 0.28 0.25 A 6.72E-05 1.19 1.09-1.30 BP: Physical position (base-pair); A1: Minor allele; F_A: Frequency of minor allele in cases; F_U: Frequency of minor allele in controls; A2: Major allele; OR: odds ratio for minor allele; 95% CI: 95% confidence intervals. 12

Chr Supplementary Table 4. Association results of 13 SNPs in the Matched discovery study, case-control validation and the combined samples. SNP b MA Matched discovery study (1,305cases vs. a Combined_Matched (5,472 cases vs. 1,444 controls) 8,640controls) c P value OR(95% CI) b MA P fix value OR fix (95% CI) P ran value OR ran (95% CI) 4 rs13117307 T 4.00E-05 1.42(1.20-1.68) T 2.82E-10 1.28(1.19-1.38) 2.82E-10 1.28(1.19-1.38) 4 rs1447045 G 3.71E-05 1.42(1.20-1.68) G 5.51E-08 1.23(1.14-1.33) 5.51E-08 1.23(1.14-1.33) 6 rs2116260 T 1.45E-05 1.27(1.14-1.42) T 2.08E-16 1.23(1.17-1.29) 1.46E-12 1.23(1.16-1.30) 6 rs4282438 G 3.10E-08 0.73(0.65-0.81) G 1.26E-26 0.75(0.72-0.79) 1.26E-26 0.75(0.72-0.79) 6 rs3117039 A 2.45E-05 1.27(1.14-1.42) A 1.38E-12 1.20(1.14-1.26) 1.38E-12 1.20(1.14-1.26) 6 rs4713607 A 6.64E-05 1.25(1.12-1.39) A 1.29E-16 1.23(1.17-1.30) 1.29E-16 1.23(1.17-1.30) 6 rs3129275 A 6.78E-07 1.32(1.18-1.47) A 6.96E-17 1.23(1.17-1.30) 5.51E-05 1.22(1.11-1.35) 6 rs3117008 C 5.14E-06 0.78(0.70-0.87) C 1.28E-22 0.78(0.74-0.82) 1.28E-22 0.78(0.74-0.82) 6 rs9391756 A 3.68E-07 0.75(0.68-0.84) A 4.15E-23 0.78(0.74-0.82) 1.64E-18 0.77(0.73-0.82) 6 rs213210 T 3.17E-06 1.30(1.16-1.45) T 5.86E-16 1.23(1.17-1.29) 1.28E-15 1.23(1.17-1.29) 6 rs9277952 A 9.70E-06 0.78(0.70-0.87) A 2.49E-10 0.85(0.81-0.89) 1.16E-04 0.86(0.80-0.93) 14 rs2295158 A 5.36E-05 1.43(1.20-1.70) A 6.31E-04 1.14(1.06-1.24) 2.27E-02 1.17(1.02-1.34) 17 rs8067378 G 5.09E-05 1.29(1.14-1.46) G 8.51E-10 1.19(1.13-1.26) 8.51E-10 1.19(1.13-1.26) a Combined_Matched: Combined results of the Matched discovery study with PCA adjustment and validations; b MA: Minor allele; c P value: PCA-adjusted P value for the samples in the Matched discovery study; P fix value: P value for the fixed effect model; P ran value: P value for the random effect model; OR fix : Odds ratio for the fixed effect model; OR ran : Odds ratio for the random effect model. 13

Supplementary Table 5. Association results of 13 SNPs in the Stringent-matched discovery study and the combined samples. Chr SNP Stringent-matched discovery study b MA (829cases vs. 990controls) c P value OR(95% CI) a Combined_Stringent-matched (4,996 cases vs. 8,186controls) b MA P fix value OR fix (95% CI) P ran value OR ran (95% CI) 4 rs13117307 T 4.97E-03 1.34(1.09-1.65) T 9.69E-09 1.26(1.16-1.36) 9.69E-09 1.26(1.16-1.36) 4 rs1447045 G 5.04E-03 1.34(1.09-1.64) G 1.41E-06 1.21(1.12-1.31) 1.41E-06 1.21(1.12-1.31) 6 rs2116260 T 1.50E-05 1.34(1.17-1.53) T 5.79E-16 1.23(1.17-1.30) 5.13E-10 1.24(1.16-1.32) 6 rs4282438 G 4.68E-09 0.66(0.58-0.76) G 4.52E-27 0.74(0.71-0.79) 1.38E-16 0.74(0.69-0.79) 6 rs3117039 A 4.76E-03 1.21(1.06-1.38) A 1.32E-10 1.19(1.13-1.25) 1.32E-10 1.19(1.13-1.25) 6 rs4713607 A 6.15E-04 1.26(1.10-1.43) A 2.01E-15 1.23(1.17-1.30) 2.01E-15 1.23(1.17-1.30) 6 rs3129275 G 6.82E-06 0.74(0.65-0.84) A 2.47E-15 1.23(1.17-1.30) 1.18E-04 1.23(1.11-1.36) 6 rs3117008 C 4.64E-05 0.76(0.67-0.87) C 1.64E-21 0.78(0.74-0.82) 1.64E-21 0.78(0.74-0.82) 6 rs9391756 A 1.86E-05 0.75(0.66-0.86) A 6.10E-21 0.78(0.74-0.82) 2.92E-17 0.78(0.73-0.82) 6 rs213210 T 1.08E-06 1.40(1.22-1.59) T 1.19E-15 1.24(1.17-1.30) 3.77E-10 1.25(1.17-1.34) 6 rs9277952 A 8.94E-05 0.76(0.67-0.87) A 2.31E-09 0.85(0.81-0.90) 2.88E-04 0.86(0.79-0.93) 14 rs2295158 A 5.09E-03 1.35(1.10-1.67) A 7.44E-03 1.12(1.03-1.21) 1.76E-02 1.14(1.02-1.27) 17 rs8067378 G 2.66E-03 1.27(1.09-1.49) G 2.00E-08 1.18(1.11-1.25) 2.00E-08 1.18(1.11-1.25) a Combined_Stringent-matched: Combined results of the Stringent-matched discovery study with PCA adjustment and validations; b MA: Minor allele; c P value: PCA-adjusted P value for the samples in the Stringent-matched discovery study; P fix value: P value for the fixed effect model; P ran value: P value for the random effect model; OR fix : Odds ratio for the fixed effect model; OR ran : Odds ratio for the random effect model. 14

Supplementary Table 6. Summary results of four SNPs in the GWAS, case-control validation and the combined samples. SNP Chr Position Locus a MA Stages OR add (95% CI) OR het (95% CI) OR hom (95% CI) rs13117307 4q12 56446497 EXOC1 T Matched discovery study 1.42 (1.20-1.68) 1.43 (1.19-1.73) 1.39 (1.01-1.91) Stringent-matched dataset 1.34 (1.09-1.65) 1.34 (1.07-1.68) 1.36 (0.89-2.09) b Follow-up 1 1.29 (1.13-1.47) 1.25 (1.08-1.44) 1.44 (1.10-1.87) Follow-up 2 1.21(1.08-1.36) 1.23(1.08-1.41) 1.15(0.92-1.44) c Combined results Matched 1.28 (1.19-1.38) 1.28 (1.17-1.39) 1.29 (1.11-1.50) d Combined results Stringent-matched 1.26 (1.16-1.36) 1.25 (1.15-1.37) 1.28 (1.09-1.50) rs8067378 17q12 35304874 GSDMB G Matched discovery study 1.29 (1.14-1.46) 1.25 (1.07-1.47) 1.31 (1.12-1.53) Stringent-matched dataset 1.27 (1.09-1.49) 1.28 (1.05-1.55) 1.27 (1.02-1.57) b Follow-up 1 1.14 (1.04-1.25) 1.15 (1.02-1.29) 1.13 (1.02-1.26) Follow-up 2 1.19(1.09-1.30) 1.22(1.09-1.36) 1.17(1.05-1.30) c Combined results Matched 1.19 (1.13-1.26) 1.20 (1.11-1.29) 1.18 (1.10-1.26) d Combined results Stringent-matched 1.18 (1.11-1.25) 1.20 (1.11-1.29) 1.16 (1.08-1.25) rs4282438 6p21.32 33180150 HLA-DPB2 G Matched discovery study 0.73 (0.65-0.81) 0.89 (0.76-1.06) 0.68 (0.60-0.76) Stringent-matched dataset 0.66 (0.58-0.76) 0.83 (0.68-1.02) 0.62 (0.53-0.72) b Follow-up 1 0.75 (0.69-0.82) 0.78 (0.69-0.89) 0.73 (0.67-0.81) Follow-up 2 0.77(0.71-0.84) 0.86(0.77-0.96) 0.74(0.68-0.81) c Combined results Matched 0.75 (0.72-0.79) 0.84 (0.78-0.90) 0.72 (0.68-0.77) d Combined results Stringent-matched 0.75 (0.71-0.79) 0.82 (0.76-0.89) 0.72 (0.68-0.76) rs9277952 6p21.32 33312252 Intergenic A Matched discovery study 0.78 (0.70-0.87) 0.74 (0.62-0.88) 0.78 (0.70-0.88) Stringent-matched dataset 0.76 (0.67-0.87) 0.74 (0.60-0.92) 0.77 (0.67-0.88) b Follow-up 1 0.92 (0.85-1.00) 0.94 (0.83-1.07) 0.91 (0.83-0.99) Follow-up 2 0.83(0.77-0.90) 0.86(0.76-0.97) 0.82(0.76-0.89) c Combined results Matched 0.85 (0.81-0.89) 0.86 (0.80-0.93) 0.84 (0.80-0.89) d Combined results Stringent-matched 0.85 (0.81-0.90) 0.87 (0.81-0.95) 0.84 (0.80-0.89) a MA: Minor allele; b Follow-up 1: Meta-analysis of Follow-up 1; ORadd: calculated in additive genetic model by logistic regression; ORhet: heterozygote versus common homozygote; ORhom: variant homozygote versus common homozygote; 95% CI: 95% confidence intervals; c Combined results: calculated with the Matched discovery study; d Combined results: calculated with the Stringent-matched discovery study. 15

Supplementary Table 7. Stepwise logistic regression analysis for independent association in GWAS. Chr SNP Position Test SNP P value Conditioned on Conditioned SNP P value 1 rs12044588 105863397 1.59E-05 NA NA 4 rs7680363 15656557 1.71E-05 0.76 rs16892888 4 rs16892888 15662277 1.02E-07 NA 4 rs749781 56430589 2.90E-05 1.00 4 rs13117307 56446497 2.59E-05 rs13117307 NA 4 rs1447045 56456305 2.36E-05 1.00 4 rs7698554 180290498 1.39E-05 NA NA 6 rs2116260 33133418 1.00E-05 0.41 6 rs7770370 33156899 6.24E-07 0.34 6 rs3128961 33158720 5.03E-06 0.21 6 rs9277535 33162839 3.36E-07 0.12 6 rs9277542 33163225 5.07E-06 0.26 6 rs3117221 33169925 9.05E-07 0.36 6 rs4282438 33180150 2.66E-08 NA 6 rs9380344 33187667 1.58E-08 0.24 rs4282438 6 rs3117039 33193829 1.96E-05 0.15 6 rs3117034 33195336 1.12E-05 0.11 6 rs9380346 33195950 1.65E-06 0.85 6 rs4713607 33198814 4.31E-05 0.64 6 rs3129275 33202236 1.53E-06 0.28 6 rs3117008 33204252 3.03E-06 0.37 6 rs7750000 33211299 6.12E-08 0.07 6 rs9391756 33223772 2.36E-07 0.16 16

6 rs9277921 33233748 1.79E-05 0.22 6 rs421446 33282761 2.93E-05 0.16 6 rs213210 33283802 1.72E-05 0.51 6 rs9277952 33312252 2.45E-06 NA NA 8 rs800574 116786624 1.60E-05 0.27 8 rs800520 116813760 1.19E-05 0.39 8 rs2694037 116863407 1.83E-06 rs2694037 NA 8 rs800544 116892787 2.97E-06 0.51 8 rs2694042 116895441 1.35E-05 0.75 9 rs7039582 96361756 6.69E-06 NA NA 10 rs3006554 30129175 8.56E-06 NA rs3006554 10 rs10826702 30135992 8.00E-05 0.11 10 rs10762170 68923895 5.74E-06 NA NA 14 rs2295158 44449239 3.82E-05 NA rs2295158 14 rs10140013 44479031 4.24E-05 0.18 17 rs72822370 32266358 3.21E-06 0.36 rs72822370 17 rs12948097 32275889 3.48E-06 NA 17 rs10445308 35191573 4.56E-06 0.67 rs8067378 17 rs8067378 35304874 1.59E-06 NA 17

Supplementary Table 9. Pair-wise LD between HLA-DP alleles tagging SNPs and two representative SNPs (rs4282438 and rs9277952). HLA Tag SNP rs4282438 rs9277952 R2 D' R2 D' P value Haplotype Freq OR Stat P value DPA1*0103 rs35953215 0.285 0.954 0.018 0.210 2.88E-03 3,3 0.359 1.18 8.99 2.72E-03 rs72879625 0.058 0.843 0.039 0.606 6.29E-01 DPA1*0201 rs34889247 0.054 0.811 0.036 0.577 5.52E-01 1,3 0.129 1.04 0.287 5.92E-01 rs3830066 0.283 0.954 0.017 0.207 2.92E-03 DPA1*0202 rs2116260 0.477 0.904 0.087 0.339 1.00E-05 2,2 0.487 0.793 19.9 8.01E-06 6-33193832 0.013 1.000 0.004 0.351 5.51E-02 DPA1*0401 rs707951 0.005 0.167 0.001 0.047 3.39E-01 2,2 0.0221 1.78 11.7 6.35E-04 6-33149985 0.009 0.794 0.012 0.799 1.28E-03 DPB1*03:01 rs7770370 0.566 0.992 0.065 0.297 6.24E-07 1,1 0.0521 1.29 4.76 2.91E-02 rs3128928 0.046 1.000 0.002 0.192 1.42E-01 DPB1*04:01 rs3135024 0.273 0.921 0.029 0.265 2.59E-03 4,1 0.0879 1.29 6.71 9.57E-03 rs3130215 0.054 1.000 0.037 0.724 6.74E-03 DPB1*05:01 rs1126513 0.149 0.992 0.063 0.570 1.71E-02 3,1 0.365 0.714 35.6 2.38E-09 rs3128961 0.434 0.949 0.089 0.379 5.03E-06 DPB1*13:01 rs6457644 0.010 0.223 0.000 0.039 8.43E-01 4,4 0.0562 1.14 1.4 2.37E-01 rs7763822 0.039 1.000 0.020 0.628 4.04E-01 DPB1*17:01 rs171329 0.001 0.058 0.002 0.050 5.10E-01 3,3 0.0432 1.25 2.51 1.13E-01 rs16868789 0.025 1.000 0.032 0.988 6.94E-02 DPB1*19:01 rs34823653 0.012 0.582 0.000 0.003 2.96E-01 4,4 0.0102 0.968 0.0175 8.95E-01 rs41288893 0.029 1.000 0.000 0.068 3.76E-01 OR: odds ratio for minor allele; Stat: Test statistic (T). 18

Supplementary Table 10. Gene expression analysis of the candidate genes between cervical cancer cases and controls from 2 available datasets. Pubmed GEO ID Gene Probe_ID FC Regulation P value Sample Description Platform 1797457 GSE7803 EXOC1 222127_s_at 1.02 DOWN 0.048 10 normal squamous cervical epitheilia GSDMB 215659_at 1.03 UP 0.274 HLA-DPB1 201137_s_at 1.04 DOWN 0.273 RING1 208371_s_at 1.01 DOWN 0.376 VPS52 214585_s_at 1.01 UP 0.534 samples and 21 invasive squamous cell carcinomas of the cervix samples 18506748 GSE9750 EXOC1 222127_s_at 1.60 DOWN 1.69E-07 24 normal squamous cervical epitheilia FC: fold change. GSDMB 215659_at 1.74 UP 0.023 HLA-DPB1 201137_s_at 1.16 DOWN 0.331 RING1 208371_s_at 1.09 DOWN 0.399 VPS52 214585_s_at 1.31 DOWN 0.007 samples and 33 invasive squamous cell carcinomas of the cervix samples Human Genome U133 Plus 2.0 Array Affymetrix Human Genome U133A Array 19

Supplementary Table 11. Expression quantitative trait loci (eqtl) analysis of rs13117307, rs8067378and rs9277952 for lymphoblastic cell lines of HAPMAP samples. HAPMAP-FEMALES CHB+JPT-FEMALES CEU-FEMALES YRI-FEMALES SNP Gene Probe BETA P value BETA P value BETA P value BETA P value rs13117307 EXOC1 GI_30410715-A -9.77E-03 8.36E-01 1.93E-02 7.90E-01-4.17E-02 6.97E-01-2.31E-02 5.83E-01 CEP135 GI_7662215-S 1.96E-02 8.13E-01 3.94E-02 6.92E-01 4.27E-03 9.70E-01-1.08E-01 2.60E-01 rs8067378 GSDMB GI_8924175-S -1.07E-01 2.85E-02-6.35E-02 2.80E-01-1.15E-01 2.04E-01-1.02E-01 3.10E-01 ZPBP2 GI_40556388-I -3.08E-03 7.17E-01-2.91E-03 8.05E-01-1.77E-02 2.94E-01 3.19E-02 6.32E-02 ORMDL3 GI_27544926-S -2.05E-01 9.47E-12-1.79E-01 7.27E-05-2.61E-01 1.62E-06-1.51E-01 1.56E-02 GSDMA GI_31342342-S 1.25E-03 8.81E-01-5.10E-03 6.84E-01 6.35E-03 7.01E-01-1.52E-02 3.43E-01 IKZF3 GI_38045964-A 6.46E-02 9.60E-02 1.65E-03 9.74E-01 1.20E-01 1.02E-01-3.48E-02 6.27E-01 PSMD3 GI_25777611-S 2.84E-02 3.54E-01 4.74E-02 3.08E-01 6.78E-04 9.90E-01 4.29E-02 5.47E-01 rs9277952 VPS52 GI_18379339-A -2.02E-02 5.58E-01-1.40E-02 7.66E-01-2.03E-02 8.52E-01 NA NA RING1 GI_11863157-S -3.67E-02 3.42E-01-2.22E-02 6.21E-01-3.68E-01 5.68E-04 NA NA RPS18 GI_14165467-S 2.70E-02 2.68E-01-3.81E-02 1.75E-01 4.41E-02 4.74E-01 NA NA HSD17B8 GI_20143980-S -5.82E-02 1.44E-01-3.36E-02 4.95E-01-2.55E-01 2.99E-02 NA NA B3GALT4 GI_15451872-S -4.98E-02 2.85E-01-1.29E-02 7.47E-01-6.49E-02 5.73E-01 NA NA SLC39A7 GI_5901935-S 5.62E-02 2.94E-01 2.18E-02 7.43E-01-2.42E-01 4.39E-02 NA NA WDR46 GI_39725662-S 3.43E-02 3.42E-01-4.45E-02 2.59E-01-3.74E-02 7.13E-01 NA NA RXRB GI_27436942-S -2.74E-02 2.96E-01-3.10E-02 4.05E-01-9.22E-02 1.89E-01 NA NA COL11A2 GI_18201914-A -3.57E-03 9.00E-01 6.05E-03 8.55E-01-1.87E-02 1.02E-01 NA NA 20

Supplementary Table 12. Association results of 11 positive SNPs in CIN samples. a Control vs. CIN a Control vs. CIN + b Cervical Cancer Chr. SNP c MA (7,196 controls vs. 729 cases) (7,196 controls vs. 4,896 cases) d F_A P value OR (95% CI) c MA d F_A P value OR (95% CI) 4 rs13117307 T 0.12 6.32E-03 1.26(1.07-1.49) T 0.12 1.40E-07 1.25(1.15-1.35) 6 rs2116260 T 0.50 7.95E-06 1.27(1.14-1.41) T 0.48 2.97E-13 1.21(1.15-1.27) 6 rs4282438 G 0.33 1.25E-07 0.73(0.65-0.82) G 0.34 2.78E-21 0.77(0.73-0.81) 6 rs3117039 A 0.42 7.96E-03 1.16(1.04-1.30) A 0.42 3.39E-09 1.18(1.11-1.24) 6 rs4713607 A 0.52 2.99E-05 1.26(1.13-1.41) A 0.51 3.15E-14 1.23(1.16-1.29) 6 rs3129275 A 0.54 1.47E-04 1.24(1.11-1.38) G 0.46 5.62E-13 0.82(0.78-0.87) 6 rs3117008 C 0.43 6.42E-06 0.77(0.69-0.87) C 0.44 2.04E-19 0.78(0.74-0.83) 6 rs9391756 A 0.40 2.18E-07 0.74(0.66-0.83) A 0.41 7.29E-19 0.79(0.74-0.83) 6 rs213210 T 0.56 6.35E-07 1.33(1.19-1.48) C 0.47 2.39E-12 0.83(0.79-0.87) 6 rs9277952 A 0.39 1.16E-02 0.87(0.77-0.97) A 0.40 3.08E-06 0.88(0.84-0.93) 17 rs8067378 G 0.29 1.57E-02 1.16(1.03-1.31) G 0.29 3.33E-06 1.15(1.08-1.22) a Control: control samples from the Follow-up 1 and 2 stages; b Cervical Cancer: cases from the Follow-up 1 and 2 stages; c MA: Minor allele; d F_A: Frequency of minor allele in cases. 21

Supplementary Table 14. Oligonucleotides used for HLA-DPA1 and HLA-DPB1 sequencing. Primer 5' sense primer(5'-3') 3' antisense primer(5'-3') HLA-DPA1 (exon 2) ACA TTT TGT CGT GTT TTT CTC T CTC TCA TCC CTT CCA GTT G HLA-DPB1 (exon 2) GAG AGT GGC GCC TCC GCT CAT GCC GGC CCA AAG CCC TCA CTC 22

Legends to excel files provided separately Supplementary Table 8. Pair-wise LD between HLA alleles (A, B, C, DQ, DR) tagging SNPs and two representative SNPs (rs4282438 and rs9277952). Supplementary Table 13. GWAS results of SNPs in previously reported candidate genes. 23

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