GWAS / Cases (n) / Controls (n) / Genotyping platform / SNPs (MAF>0.03)
North American / 1,330 / 2,042 / Illumina 610K/317K / 2,508,744
UK (phase I) / 866 / 2,354 / Illumina 610K/550K / 2,508,744
COGS / 7,035 / 21,693 / Illumina custom iSelect / 7,768,381
Supplementary Table S2. Genes in the six significant co-expression networks
Hub TF: HOXB2 / Hub TF: HOXB7 / Hub TF: HOXB6 / Hub TF: HOXD3 / Hub TF: HOXB5 / Hub TF: HOXD1
HOXD3 / HOXD3 / HOXD3 / HOXB6 / HOXD3 / BNC2
SKAP1 / SKAP1 / HOXB5 / HOXB5 / HOXB6 / HOXD3
HOXB6 / HOXB6 / HOXB9 / LRRC17 / HOXB9 / HOXB5
HOXB5 / ABHD8 / HOXB3 / HOXB9 / HOXB3 / DOK5
HOXB9 / HOXB5 / HOXB2 / DOK5 / HOXB2 / HOXD9
HOXB3 / HOXB9 / HNF1B / MDFI / HOXB7 / DACH1
HOXB7 / HOXB3 / HOXB7 / HOXB3 / HOXD1 / MTX2
PNPO / HOXB2 / COPZ2 / HOXB2 / ST8SIA2 / ZNF217
SCPEP1 / HNF1B / ETV1 / HOXB7 / SCG2 / ZNF219
GPR125 / SLC35B1 / TNFAIP6 / APOL2 / MSX2 / DTX3
MYST2 / SP2 / BLNK / HOXD9 / KCNA1 / DUSP10
RSBN1 / GATA6 / FLJ23049 / MTX2 / GATA6 / NSUN3
SNF8 / SNX11 / MSX2 / HOXD1 / HOXA2 / RNASE1
NDUFS2 / AKAP7 / MNX1 / DLX5 / DPT / MMD
POU2AF1 / SPOP / RARG / GAK / HOXA4 / EVL
CALCOCO2 / OXTR / CALB2 / NUDT4 / HOXA5 / GFRA2
FLJ20920 / RBM5 / MMP11 / HOXA7 / ZNF141 / EDG7
VAMP4 / OXTR / GFRA2 / CXCL14 / TNNT2
FLNA / COL3A1 / ALCAM / ALDH1A3 / CLDN10
TUBD1 / SPHK1 / KCNIP1 / LRRC15 / ACPP
DDX52 / CXCL14 / RNF4 / TMEM158 / CSF1
SNF8 / ASXL1 / GATA6 / COL6A3 / APOL1
CNN2 / FGF1 / WT1 / COL1A1 / MRPL33
VPS72 / CCNA1 / LHX1 / CMTM6 / PDYN
HBEGF / KIF26B / CFTR / GREM1 / WT1
ZNF34 / PRRX1 / GOLIM4 / TNR / LHX1
TDRKH / TFCP2L1 / TCF7L1 / NNMT / MAPK7
SLC15A1 / PEG3 / PLXNA3 / DIO2 / TCF7L1
KCNMB4 / GREM1 / OTUD4 / TACR3 / SAMHD1
TCTN2 / PVALB / IGFBP4 / COL5A2 / BMP2
ST8SIA1 / NDST3 / FSHR / SLC22A17
KCNMB4 / HOXA5 / GJB1
COL5A2 / NR4A2 / WISP3
SCN9A / PCK1
MTCP1 / PAMCI
CLDN11 / EPB49
NEDD9 / CDK6
CD55 / TMEM165
Supplementary Table S2. Genes in the six significant co-expression networks (continued)
Hub TF: HOXB2 / Hub TF: HOXB7 / Hub TF: HOXB6 / Hub TF: HOXD3 / Hub TF: HOXB5 / Hub TF: HOXD1
ID2 / PAK3
SDC1 / GRSF1
FASTKD1 / EMX2
TRDMT1 / SORBS3
E2F2 / ROR1
SDC2 / TMEM140
STAMBP / POMGNT1
GSTM3 / CNKSR1
NDST3 / SRD5A2L
ATP10B / GLI2
GDAP1 / CD55
GAB2 / HTR3A
LOXL1 / LAP3
CENPC1 / HCG_40738
XK
DPP3
BMP4
FAM130A2
SLIT3
BMP7
PSCD3
GSTM3
COL18A1
RHOBTB3
CBX6
ITGAV
PFTK1
IL6R
SMO
TM4SF1
CHODL
Leading edge subset genes are in bold type. All genes are listed in the order in which they appear in the ranked list prepared from the GWAS meta-analysis results.
Supplementary Table S3. GSEA results for 14 serous EOC risk locus TF-centric gene co-expression networks: genes ranked after LD-based clumping of SNPsa
Serous EOC / Network hub / Co-expression / Normalized / Nominal / FDR / Top 5%
risk locus / TF gene / network size / enrichment / p Value / q-value / fold enrichment
17q21.32 / HOXB2 / 17 / 1.94 / 0b / 0b / 8.00
17q21.32 / HOXB7 / 29 / 1.85 / 0b / 2.0E-05b / 4.00
17q21.32 / HOXB6 / 33 / 1.58 / 1.2E-03 / 3.7E-03 / 4.00
2q31 / HOXD3 / 51 / 1.54 / 6.0E-04 / 5.3E-03 / 3.33
17q21.32 / HOXB5 / 29 / 1.47 / 9.2E-03 / 0.01 / 2.50
2q31 / HOXD1 / 68 / 1.43 / 1.7E-03 / 0.02 / 1.50
17q21.32 / TBX21 / 41 / 1.15 / 0.21 / 0.29 / 1.00
17q21.32 / SP2 / 122 / 1.12 / 0.15 / 0.33 / 1.14
17q21.32 / HOXB3 / 100 / 1.12 / 0.17 / 0.30 / 2.00
19p13 / NR2F6 / 296 / 1.11 / 0.08 / 0.28 / 1.00
8q24 / MYC / 122 / 1.01 / 0.47 / 0.60 / 0.57
17q21.32 / NFE2L1 / 301 / 0.99 / 0.57 / 0.63 / 0.88
2q31 / HOXD10 / 83 / 0.98 / 0.56 / 0.61 / 0.40
3q25 / SHOX2 / 357 / 0.96 / 0.72 / 0.63 / 1.06
aHub-and-spoke networks containing 15 to 500 genes constructed from serous EOC TCGA data.
bFor 50,000 permutations since nominal P-value = 0 at the default number of 10,000 permutations.
Supplementary Table S4. Replication results (GSEA) using COGS GWAS
for the six networks significant in the primary analysis
Serous EOC / Network hub / Co-expression / Normalized / Nominal
risk locus / TF gene / network size / enrichment / P-value
2q31 / HOXD1 / 69 / 1.34 / 4.0E-04
17q21.32 / HOXB5 / 32 / 1.46 / 1.0E-03
17q21.32 / HOXB7 / 34 / 1.44 / 1.3E-03
17q21.32 / HOXB6 / 35 / 1.40 / 1.7E-03
17q21.32 / HOXB2 / 20 / 1.44 / 3.6E-03
2q31 / HOXD3 / 54 / 1.19 / 3.4E-02
Supplementary Table S5. GSEA results for the 24 co-expression networks
containing > 10 genes (including 10 networks with > 500 genes)
Serous EOC / Network hub / Co-expression / Normalized / Nominal / FDR
risk locus / TF gene / network size / enrichment / P-value / q-value
17q21.32 / HOXB2 / 17 / 1.63 / 1.0E-04 / 1.0E-04
17q21.32 / HOXB7 / 31 / 1.62 / 0a / 5.0E-05
17q21.32 / HOXB6 / 33 / 1.44 / 7.0E-04 / 2.0E-03
2q31 / HOXD3 / 52 / 1.39 / 2.0E-04 / 5.1E-03
17q21.32 / HOXB5 / 30 / 1.37 / 4.4E-03 / 5.5E-03
2q31 / HOXD1 / 69 / 1.25 / 8.6E-03 / 0.04
17q21.32 / HOXB3 / 103 / 1.18 / 0.02 / 0.09
17q21.32 / SP2 / 134 / 1.18 / 0.01 / 0.08
17q21.32 / TBX21 / 46 / 1.11 / 0.18 / 0.21
17q21.32 / NFE2L1 / 315 / 1.06 / 0.12 / 0.37
17q21.32 / HOXB8 / 763 / 1.04 / 0.12 / 0.49
19p13 / NR2F6 / 312 / 1.04 / 0.23 / 0.47
17q21.32 / HOXB1 / 1727 / 1.03 / 0.13 / 0.54
8q24 / MYC / 130 / 1.03 / 0.36 / 0.51
2q31 / HOXD12 / 1677 / 1.02 / 0.16 / 0.50
2q31 / HOXD13 / 1568 / 1.02 / 0.23 / 0.52
19p13 / KLF2 / 706 / 1.02 / 0.32 / 0.51
2q31 / HOXD11 / 907 / 1.02 / 0.30 / 0.49
17q21.32 / HOXB9 / 761 / 1.01 / 0.39 / 0.53
3q25 / SHOX2 / 368 / 1.00 / 0.52 / 0.63
17q21.32 / HOXB13 / 1433 / 1.00 / 0.56 / 0.61
2q31 / HOXD10 / 85 / 0.99 / 0.52 / 0.59
5p15 / IRX4 / 1477 / 0.99 / 0.62 / 0.59
17q12 / HNF1B / 1137 / 0.98 / 0.73 / 0.64
aFor 50,000 permutations, since nominal P-value = 0 at the default number of
10,000 permutations.
Supplementary Table S6: Number of intragenic SNPs and genes covered by them in the TCGA unified expression data set
SNP list used / Genes covered (of 11,864) / Number of
for ranking genes / from TCGA / intragenic SNPs
GWAS meta-analysis / 10,693 / 689,882
LD-thinned GWAS meta / 10,225 / 183,567
COGS GWAS / 11,113 / 1,982,169
AB
Supplementary Figure S1: Quantile-quantile plots of the minimum P-value among all SNPs mapping to each gene (A) without correction and (B) after applying the modified Sidak correction for the number of SNPs in each gene. The grey funnel represents 95% confidence intervals for the expected P-values.
Supplementary Figure S2: Largest single connected component from DAPPLE output. Also shown is the second largest single connected component. Input genes/proteins are colored according to their individual connectivity P-values calculated by DAPPLE. Grey nodes are proteins not in input that interact with at least two input proteins.