Table S1: Characteristics of 1,610 invasive epithelial ovarian cancer cases and controls in discovery set North Carolina Ovarian Cancer Study Mayo Clinic (MAY) (NCO) Characteristics* Cases Controls Cases Controls (n=328) (n=459) P-value† (n=343) (n=480) P-value† n (%) n (%) n (%) n (%) Age, y [mean (SD)] 60.9 (12.6) 60.1 (13.0) 0.36 56.8 (10.4) 54.7 (12.0) 0.008 Body mass index, kg/m2 <23 66 (20.8) 106 (24.7) 96 (29.0) 132 (28.2) 23-26 74 (23.3) 121 (28.1) 85 (25.7) 117 (25.0) 26-29 78 (24.6) 109 (25.3) 75 (22.7) 110 (23.5) ≥29 99 (31.2) 94 (21.9) 0.03 75 (22.7) 109 (23.3) 0.98 Oral contraceptive use, mo Never 154 (49.5) 164 (38.7) 116 34.5) 148 (31.0) 1-48 79 (25.4) 90 (21.2) 105 (31.3) 133 (27.9) ≥48 78 (25.1) 170 (40.1) <0.001 115 (34.2) 196 (41.1) 0.14 Postmenopausal hormone use, mo Never 193 (61.7) 243 (58.6) 108 (33.4) 270 (59.3) 1-60 57 (18.2) 78 (18.8) 114 (35.3) 96 (21.1) ≥60 63 (20.1) 94 (22.7) 0.65 101 (31.3) 89 (19.6) <0.001 Parity, n/age at first birth, y Nulliparous 56 (17.5) 64 (14.8) 71 (20.7) 64 (13.3) 1-2/≤20 21 (6.6) 25 (5.8) 46 (13.4) 57 (11.9) 1-2/≥20 92 (28.7) 129 (29.9) 125 (36.4) 211 (44.0) ≥3/≤20 60 (18.8) 63 (14.6) 49 (14.3) 61 (12.7) ≥3/≥20 91 (28.4) 151 (35.0) 0.24 52 (15.2) 87 (18.1) 0.02 Histology Serous 201 (61.5) 206 (60.2) Mucinous 9 (2.7) 19 (5.6) Endometrioid 62 (19.0) 53 (15.5) Clear Cell 22 (6.7) 28 (8.2) Other 33 (10.1) 36 (10.5) * Data are counts (percentage) unless otherwise indicated. † P-values are based upon t test (continuous variables) and χ2 test (categorical variables).

1 Table S2: Characteristics of 1,923 invasive epithelial ovarian cancer cases and controls in replication set Brigham & Women’s Hospital Study Tampa Bay Ovarian Cancer Study Familial Ovarian Tumor Study (BWH) (TBO) (TOR) Characteristics* Cases Controls Cases Controls Cases Controls (n=133) (n=142) P-value † (n=227) (n=163) P-value† (n=734) (n=524) P-value †

Age, y [mean (SD)] 63.2 63.5 0.75 61.5 59.7 0.12 61.0 54.8 <0.001 Histology Serous 132 (99.3) 146 (64.3) 401 (54.6) Mucinous 0 (0) 13 (5.7) 57 (7.8) Endometrioid 0 (0) 28 (12.3) 154 (21.0) Clear Cell 0 (0) 12 (5.3) 47 (6.4) Other 1 (0.7) 28 (12.3) 75 (10.2) * Data are counts (percentage) unless otherwise indicated. † P-values are based upon t test (continuous variables)

2 Table S3. included in discovery SNP analysis of ovarian cancer risk Number of SNPs genotyped BEST4 2 1 BUB1 1 2 BUB1B 6 15 CDC2L5 8 7 CDC7 8 1 CDK6 24 7 CIT 13 12 CLK2 1 1 CSNK2A1 8 20 DCTN5 2 16 FYN 8 6 GSG2 1 17 ITGAE 1 17 ITIH1 1 3 KIAA0999 18 11 LATS1 1 6 LATS2 14 13 LOC440587 1 1 LOC613206 3 9 LOC645967 1 6 LOC646050 1 2 LOC647195 6 1 LOC653303 1 11 LOC728541 1 6 LOC729119 1 19 LRRK1 12 15 MAPKAPK2 9 1 MARK1 11 1 MARK2 6 11 MAST1 2 19 MAST2 10 1 MASTL 9 10 METTL2A 1 17

3 Gene Number of SNPs genotyped Chromosome NEK2 10 1 NEK3 3 13 NEK4 3 3 NEK6 9 9 NEK7 7 1 NEK8 1 17 NEK9 2 14 NLK 10 17 PBK 6 8 PCTK1 1 X PKMYT1 1 16 PKN2 12 1 5 16 PLK2 7 5 PLK4 2 4 PRKACB 22 1 PRKG2 10 4 RAD51C 1 17 ROCK1 6 18 ROCK2 10 2 RTBDN 3 19 RYK 8 3 SCYL3 12 1 SHC1 3 1 STK11 1 19 STK4 13 20 TEX14 8 17 TLCD1 1 17 TLK2 5 17 TMED10 1 14 TOMM34 2 20 TRIB3 9 20 TTK 4 6 7 11

4 Table S4. Discovery single SNP associations with risk of invasive ovarian cancer in a log-additive model (p<0.05) Serous All subtypes Gene Chr MAF SNP OR 95% CI P-value† OR 95% CI P-value† CDC7 1 0.17 rs13447553 0.74 (0.58 - 0.95) 0.019 0.86 (0.70 - 1.06) 0.149 MARK1 1 0.09 rs3737297 0.73 (0.51 - 1.04) 0.08 0.69 (0.51 - 0.92) 0.011 1 0.07 rs17007981 0.73 (0.50 - 1.08) 0.114 0.68 (0.50 - 0.93) 0.0167 MAST2 1 0.44 rs11579634 0.83 (0.70 – 1.00) 0.044 0.85 (0.73 - 1.00) 0.049 NEK2 1 0.03 rs11119790 1.52 (1.00 - 2.31) 0.049 1.3 (0.89 - 1.91) 0.17 NEK7 1 0.1 rs12060034 0.82 (0.59 - 1.14) 0.236 0.76 (0.58 - 0.99) 0.0404 SCYL3 1 0.17 rs4656198 1.23 (0.97 - 1.56) 0.084 1.28 (1.06 - 1.55) 0.0108 NEK4 3 0.05 rs17477867 1.46 (1.03 - 2.07) 0.034 1.44 (1.07 - 1.95) 0.0169 PRKG2 4 0.04 rs17484474 0.59 (0.36 - 0.97) 0.039 0.77 (0.52 - 1.16) 0.21 PLK2 5 0.11 rs12513877 1.16 (0.88 - 1.53) 0.285 1.34 (1.08 - 1.66) 0.00857 5 0.14 rs7736949 1.15 (0.90 - 1.46) 0.272 1.29 (1.06 - 1.57) 0.0104 5 0.11 rs1042994 1.16 (0.88 - 1.52) 0.301 1.3 (1.04 - 1.61) 0.0195 CDK6 7 0.07 rs2282990 1.71 (1.25 - 2.34) 8.2 x 10-4 1.61 (1.22 - 2.12) 6.7 x 10-4 7 0.05 rs3731348 1.46 (1.04 - 2.05) 0.031 1.23 (0.90 - 1.70) 0.192 7 0.07 rs17690388 0.67 (0.46 - 0.98) 0.038 0.76 (0.54 - 1.05) 0.094 7 0.35 rs2282983 1.2 (1.01 - 1.43) 0.039 1.15 (0.98 1.34) 0.085 7 0.22 rs7781436 0.81 (0.65 - 1.01) 0.057 0.83 (0.70 – 1.00) 0.0488 SIK3 11 0.22 rs7928320 0.76 (0.61 - 0.93) 8.4 x 10-3 0.8 (0.67 - 0.95) 0.0117 11 0.38 rs573549 0.82 (0.68 - 0.98) 0.025 0.84 (0.72 - 0.98) 0.029 11 0.36 rs10892052 0.83 (0.70 – 1.00) 0.046 0.86 (0.74 - 1.01) 0.072 11 0.07 rs525302 0.71 (0.48 - 1.06) 0.092 0.65 (0.47 - 0.91) 0.0107 NEK3 13 0.37 rs6561658 0.93 (0.77 - 1.11) 0.417 0.83 (0.72 - 0.97) 0.0159 NEK9 14 0.1 rs12883497 1.15 (0.85 - 1.54) 0.371 1.33 (1.06 - 1.68) 0.0151 BUB1B 15 0.31 rs1047130 1.18 (0.98 - 1.43) 0.079 1.19 (1.02 - 1.39) 0.0231 LRRK1 15 0.26 rs12915781 0.9 (0.73 - 1.11) 0.315 0.84 (0.71 – 1.00) 0.0444 NEK8 17 0.07 rs17720826 1.43 (1.03 - 1.98) 0.035 1.27 (0.94 - 1.70) 0.12

5 Serous All subtypes Gene Chr MAF SNP OR 95% CI P-value† OR 95% CI P-value† NLK 17 0.19 rs2125846 1.35 (1.09 - 1.66) 6.0 x 10-3 1.28 (1.07 - 1.54) 0.00723 17 0.09 rs10512429 1.39 (1.04 - 1.85) 0.026 1.3 (1.02 - 1.66) 0.0358 TEX14 17 0.06 rs12944693 1.49 (1.07 - 2.08) 0.02 1.52 (1.14 - 2.04) 0.00425 17 0.22 rs9303399 1.23 (1.01 - 1.50) 0.041 1.22 (1.03 - 1.45) 0.0235 RTBDN 19 0.15 rs4804736 1.2 (0.94 - 1.53) 0.146 1.26 (1.04 - 1.54) 0.0195 CSNK2A 20 0.09 rs6107514 0.68 (0.49 - 0.96) 0.028 0.9 (0.68 - 1.19) 0.465 STK4 20 0.23 rs927000 0.81 (0.65 – 1.00) 0.05 0.87 (0.72 - 1.04) 0.133 20 0.15 rs13038635 1.19 (0.94 - 1.52) 0.146 1.24 (1.02 - 1.51) 0.0304 20 0.29 rs6073582 1.18 (0.97 - 1.44) 0.089 1.18 (1.01 - 1.38) 0.0409 TRIB3 20 0.17 rs9941773 0.76 (0.59 - 0.97) 0.027 0.85 (0.69 - 1.05) 0.133 * Adjusted for age, geographic location, body mass index (BMI), oral contraceptive (OC) use, hormone-replcaement therapy (HRT), and parity/age at first birth. † Based on a test for trend. Associations with p<0.05 are in bold. MAF, minor allele frequency.

6 Table S5. Haplotype associations with risk of serous invasive ovarian cancer for CDK6, SIK3, TEX14, and NLK in discovery study a) CDK6 haplotypes Haplotypes rs2282990 rs3731348 rs17690388 rs2282983 Frequency (%) OR (95% CI) P value

1 C G G T 0.58 1.00 2 C G G C 0.28 1.01 (0.82 – 1.24) 0.95 3 C G A T 0.059 0.63 (0.40 – 0.99) 0.044 4 T T G C 0.057 1.38 (0.92 – 2.05) 0.12 5 T G G C 0.020 2.42 (1.30 – 4.50) 0.0054 Global haplotype association 0.0034

Rare estimated haplotypes (cumulative frequency = 0.0069) not shown.

b) SIK3 haplotypes Haplotypes rs7928320 rs573549 rs10892052 Frequency (%) OR (95% CI) P value

1 C G A 0.63 1.00 2 T A G 0.21 0.66 (0.52 – 0.84) 0.0007 3 C A G 0.13 0.97 (0.74 – 1.28) 0.84 4 C A A 0.019 0.71 (0.31 – 1.48) 0.36 Global haplotype association 0.0014

Rare estimated haplotypes (cumulative frequency = 0.0089) not shown.

c) TEX14 haplotypes Haplotypes rs12944693 rs9303399 Frequency (%) OR (95% CI) P value

1 T G 0.77 1.00 2 T A 0.16 1.09 (0.85 – 1.39) 0.51 3 C A 0.069 1.63 (1.14 – 2.33) 0.0074 Global haplotype association 0.028

7 c) NLK haplotypes Haplotypes rs2125846 rs10512429 Frequency (%) OR (95% CI) P value

1 A G 0.80 1.00 2 G G 0.11 1.30 (0.97 – 1.74) 0.084 3 G A 0.010 1.35 (0.99 – 1.85) 0.061 Global haplotype association 0.056

8 Table S6. Single SNP associations with risk of invasive ovarian cancer in replication study Serous ovarian cancers All ovarian cancers Gene SNP OR† 95% CI P-value‡ OR† 95% CI P-value‡ BUB1B rs1047130* 0.94 (0.77 - 1.15) 0.27 0.99 (0.83 - 1.18) 0.46 CDC7 rs13447553* 1.07 (0.83 - 1.38) 0.30 1.00 (0.79 - 1.25) 0.49 CDK6 rs17690388* 0.64 (0.40 - 1.01) 0.029 0.76 (0.51 - 1.12) 0.082 rs2282983 0.94 (0.79 - 1.11) 0.23 0.92 (0.79 - 1.07) 0.14 rs2282990* 1.15 (0.87 - 1.50) 0.16 1.16 (0.92 - 1.48) 0.11 rs3731348 1.43 (1.02 - 1.99) 0.018 1.31 (0.98 - 1.73) 0.033 rs7781436 0.95 (0.79 - 1.15) 0.31 1.02 (0.87 - 1.21) 0.38 CSNK2A rs6107514 0.97 (0.74 - 1.28) 0.43 0.89 (0.70 - 1.14) 0.18 LRRK1 rs12915781 1.08 (0.89 - 1.31) 0.23 1.03 (0.87 - 1.22) 0.35 MARK1 rs17007981* 0.89 (0.68 - 1.18) 0.22 0.93 (0.72 - 1.19) 0.28 rs3737297 1.01 (0.79 - 1.30) 0.47 0.99 (0.79 - 1.24) 0.47 MAST2 rs11579634* 0.91 (0.78 - 1.06) 0.11 0.94 (0.83 - 1.07) 0.19 NEK2 rs11119790 1.45 (0.94 - 2.23) 0.046 1.19 (0.82 - 1.74) 0.18 NEK3 rs6561658* 1.05 (0.90 - 1.24) 0.26 1.02 (0.89 - 1.18) 0.37 NEK4 rs17477867 1.05 (0.75 - 1.46) 0.39 0.93 (0.69 - 1.24) 0.31 NEK7 rs12060034* 0.92 (0.71 - 1.20) 0.28 0.88 (0.70 - 1.11) 0.14 NEK8 rs17720826 1.21 (0.87 - 1.68) 0.12 1.06 (0.79 - 1.42) 0.35 NEK9 rs12883497 1.09 (0.83 - 1.41) 0.27 1.03 (0.82 - 1.29) 0.41 NLK rs10512429 1.27 (1.00 - 1.62) 0.027 1.21 (0.97 - 1.51) 0.044 rs2125846* 1.36 (1.11 - 1.67) 0.00177 1.30 (1.08 - 1.56) 0.00297 PLK2 rs1042994 0.98 (0.78 - 1.23) 0.43 0.93 (0.76 - 1.14) 0.25 rs12513877* 1.19 (0.75 - 1.87) 0.23 1.18 (0.79 - 1.77) 0.21 rs7736949* 0.98 (0.79 - 1.20) 0.41 1.00 (0.83 - 1.21) 0.48 PRKG2 rs17484474* 1.07 (0.69 - 1.66) 0.38 1.04 (0.71 - 1.53) 0.42 RTBDN rs4804736* 1.13 (0.91 - 1.39) 0.13 1.07 (0.89 - 1.29) 0.23 SCYL3 rs4656198* 0.96 (0.79 - 1.16) 0.34 0.99 (0.83 - 1.16) 0.43 SIK3 rs10892052 1.11 (0.94 - 1.32) 0.12 1.06 (0.91 - 1.23) 0.23 rs525302* 0.80 (0.56 - 1.15) 0.11 0.82 (0.60 - 1.11) 0.10 rs573549* 1.10 (0.94 - 1.28) 0.12 1.06 (0.92 - 1.21) 0.21 rs7928320 1.08 (0.87 - 1.33) 0.24 1.04 (0.87 - 1.25) 0.33 STK4 rs13038635 0.98 (0.80 - 1.20) 0.42 1.01 (0.85 - 1.20) 0.45 rs6073582* 1.05 (0.88 - 1.26) 0.29 1.02 (0.87 - 1.19) 0.40 rs927000* 0.90 (0.72 - 1.11) 0.16 0.94 (0.78 - 1.13) 0.25 TEX14 rs12944693 1.04 (0.74 - 1.46) 0.41 1.08 (0.81 - 1.45) 0.29 rs9303399* 1.02 (0.84 - 1.22) 0.44 1.05 (0.89 - 1.24) 0.28 TRIB3 rs9941773* 0.95 (0.74 - 1.21) 0.34 1.00 (0.81 - 1.24) 0.49 * Imputed. † Log-additive model adjusted for age and study site (BWH, TBO, TOR). ‡ One-sided p-values. Associations of interest (p<0.05) in bold.

9 Table S7. Minor allele frequencies among controls by study for rs2125846, rs3731348, and rs10512429

Study rs2125846 rs3731348 rs10512429 MAY 0.186 0.054 0.098 NCO 0.194 0.052 0.083 BWH 0.170 0.109 0.106 TBO 0.123 0.052 0.064 TOR 0.162 0.056 0.094 Combined 0.174 0.058 0.090

10