Background
Methods
Study sample
Cancer phenotype definitions and residual creation
Genotyping
Statistical Analysis
Association
Phenotype* | Traits | Number of participants | Events | Adjustment (database phenotype variable name) |
---|---|---|---|---|
All Cancer* (excluding non-melanoma skin cancer) | 2 | 1335 | 250 | Cohort- and sex-specific 1. age at study entry (allcancer1) 2. multivariable adjusted for age, body mass index, and cigarette smoking at study entry (allcancer2) |
Breast Cancer (women) | 2 | 723 | 58 | Cohort-specific 1. age at study entry (breastcancer1) 2. multivariable adjusted for age, parity, and body mass index at study entry (breastcancer2) |
Prostate Cancer (men) | 1 | 617 | 59 | Cohort-specific 1. age at study entry (prostatecancer1) |
SNP prioritization
Results
2a. GEE results ranked by p-value | |||||
---|---|---|---|---|---|
SNP | Chr | Physical Position | GEE p-value | FBAT p-value | Gene region (within 60 kb) |
BREAST CANCER
| |||||
rs2075555 | 17 | 45,629,290 |
8.3 × 10
-8
| 0.157 |
COL1A1
|
rs6556756 | 5 | 163,821,858 |
5.0 × 10
-7
| 0.114 | |
rs1154865 | 12 | 72,276,104 |
6.6 × 10
-7
| 0.052 | |
rs1978503 | 18 | 51,815,280 |
9.66 × 10
-7
| 0.287 | |
rs1926657 | 13 | 94,672,957 |
1.9 × 10
-6
| 0.072 |
ABCC4
|
rs10263639 | 7 | 66,503,417 |
2.7 × 10
-6
| 0.590 | |
rs10490113 | 2 | 59,410,998 |
4.7 × 10
-6
| 0.077 | |
rs458685 | 21 | 30,099,382 |
6.0 × 10
-6
| 0.064 |
GRIK1
|
rs1876206 | 15 | 46,687,878 |
6.0 × 10
-6
| 0.742 |
FBN1
|
rs9314033 | 5 | 163,822,784 |
1.2 × 10
-5
| 0.058 | |
rs10486490 | 7 | 25,846,789 |
1.3 × 10
-5
| 0.245 | |
rs9325024 | 5 | 146,185,979 |
1.7 × 10
-5
| 0.112 |
PPP2R2B
|
rs1294255 | 1 | 229,808,093 |
1.9 × 10
-5
| 0.470 | |
rs10513754 | 3 | 178,681,862 |
2.8 × 10
-5
| 0.189 | |
rs10501093 | 11 | 27,946,695 |
3.0 × 10
-5
| 0.066 |
KIF18A
|
PROSTATE CANCER
| |||||
rs9311171 | 3 | 37,971,481 |
1.8 × 10
-6
| 0.392 |
CTDSPL
|
rs1529276 | 13 | 102,726,008 |
1.8 × 10
-6
| 0.071 | |
rs10498792 | 6 | 51,774,590 |
3.0 × 10
-6
| 0.285 |
PKHD1
|
rs4466137 | 5 | 83,021,495 |
3.1 × 10
-6
| 0.305 |
HAPLN1
|
rs345013 | 3 | 146,656,486 |
5.1 × 10
-6
| 0.002 | |
rs10505137 | 8 | 111,210,785 |
1.3 × 10
-5
| 0.002 | |
rs1873038 | 3 | 175,020,343 |
1.8 × 10
-5
| 0.317 |
NLGN1
|
rs8019932 | 14 | 29,676,177 |
1.9 × 10
-5
| 0.019 | |
rs344985 | 3 | 146,619,475 |
2.1 × 10
-5
| 0.002 | |
rs1920676 | 11 | 15,789,323 |
2.2 × 10
-5
| 0.196 | |
rs10511206 | 10 | 127,209,365 |
2.4 × 10
-5
| 0.028 | |
rs1037569 | 5 | 119,954,204 |
2.8 × 10
-5
| 0.165 | |
rs2109312 | 2 | 128,292,061 |
3.0 × 10
-5
| 0.786 |
WDR33
|
rs1352416 | 3 | 174,963,409 |
3.4 × 10
-5
| 0.201 |
NLGN1
|
rs1440714 | 11 | 15,,790,399 |
3.7 × 10
-5
| 0.223 | |
2b. FBAT results ranked by p-value
| |||||
SNP
|
Chr
|
Physical Position
|
GEE p-value
|
FBAT p-value
|
Gene Region (within 60 kb)
|
BREAST CANCER
| |||||
rs7711990 | 5 | 180,307,504 | 0.010 |
8.4 × 10
-5
| |
rs1451125 | 4 | 137,449,995 | 0.008 |
9.5 × 10
-5
| |
rs4266352 | 4 | 109,823,951 | 0.001 |
1.2 × 10
-4
| |
rs6720918 | 2 | 122,873,276 | 0.027 |
1.9 × 10
-4
| |
rs6101183 | 20 | 59,025,355 | 0.132 |
2.0 × 10
-4
| |
rs9307064 | 4 | 90,503,827 | 0.159 |
2.2 × 10
-4
| |
rs10512287 | 9 | 101,538,523 | 0.807 |
2.3 × 10
-4
|
GRIN3A
|
rs7190881 | 16 | 7,368,424 | 0.475 |
2.9 × 10
-4
| |
rs2224402 | 1 | 229,359,076 | 0.418 |
3.1 × 10
-4
|
C1orf57
|
rs10516690 | 4 | 84,822,792 | 0.954 |
3.7 × 10
-4
| |
rs10487920 | 7 | 145,895,727 | 0.085 |
3.9 × 10
-4
|
CNTNAP2
|
rs6479347 | 9 | 91,348,121 | 0.017 |
4.5 × 10
-4
| |
rs1924587 | 13 | 96,195,380 | 0.020 |
4.6 × 10
-4
|
HS6ST3
|
rs2059273 | 16 | 5,991,144 | 0.005 |
4.9 × 10
-4
|
A2BP1
|
rs2822669 | 21 | 14,752,449 | 0.029 |
5.7 × 10
-4
|
SAMSN1
|
PROSTATE CANCER
| |||||
rs657057 | 6 | 56,402,241 | 0.109 |
3.4 × 10
-5
|
DST
|
rs6691482 | 1 | 170,274,521 | 0.007 |
4.0 × 10
-5
|
SLC9A11
|
rs4378061 | 9 | 10,930,127 | 0.633 |
6.6 × 10
-5
| |
rs2056387 | 1 | 234,250,153 | 0.159 |
1.1 × 10
-4
|
RYR2
|
rs2274626 | 1 | 176,253,589 | 0.005 |
1.4 × 10
-4
|
NPHS2
|
rs181247 | 17 | 53,562,730 | 0.552 |
3.2 × 10
-4
|
OR4D1|OR4D2
|
rs7827348 | 8 | 3,020,222 | 0.054 |
3.6 × 10
-4
| |
rs255561 | 5 | 82,386,566 | 0.040 |
3.9 × 10
-4
|
XRCC4
|
rs1504858 | 4 | 137,063,555 | 0.010 |
3.9 × 10
-4
| |
rs954709 | 4 | 167,317,424 | 0.049 |
4.2 × 10
-4
| |
rs2179443 | 20 | 37,450,516 | 0.057 |
4.4 × 10
-4
| |
rs35239 | 5 | 68,064,834 | 0.657 |
4.6 × 10
-4
| |
rs477516 | 8 | 16,758,362 | 0.057 |
5.1 × 10
-4
| |
rs595725 | 1 | 28,993,331 | 0.239 |
5.3 × 10
-4
|
OPRD1
|
rs10515322 | 5 | 101,539,543 | 0.051 |
5.4 × 10
-4
|
SLCO4C1
|
Associations within Candidate Genes Selected by Cancer Type: FBAT or GEE p-value < 0.01 | ||||||
---|---|---|---|---|---|---|
Cancer Trait | Gene | SNP | Chr | Physical Position | GEE p-value | FBAT p-value |
Breast cancer |
ERBB4
| rs905883 | 2 | 213,013,976 | 2.0 × 10-4 | 0.8517 |
Breast cancer |
ERBB4
| rs7564590 | 2 | 213,213,406 | 0.0032 | 0.2567 |
Breast cancer |
ERBB4
| rs7558615 | 2 | 212,771,655 | 0.008 | 0.8457 |
Prostate cancer |
MSR1
| rs9325782 | 8 | 16,134,844 | 8.2 × 10-4 | 0.3448 |
Prostate cancer |
MSR1
| rs2410373 | 8 | 15,968,877 | 0.014 | 0.02051 |
SNP | Physical Position | Distance from reported marker | MAF | GEE p-value | FBAT p-value |
---|---|---|---|---|---|
rs7001069 | 128179828 | -253268 | 0.0188 | 3.0 × 10-5 | 0.39322 |
rs10505483 | 128194377 | -238719 | 0.0223 | 4.0 × 10-5 | 0.32697 |
rs1562871 | 128470954 | 37858 | 0.1696 | 0.16618 | 0.00328 |
rs10505474 | 128486686 | 53590 | 0.406 | 0.00995 | 0.0121 |
rs10505506 | 129114473 | 681377 | 0.3275 | 0.00829 | 0.92941 |
CGEMS Phase 1a | FHS 100K | |||||||||
---|---|---|---|---|---|---|---|---|---|---|
DBSNP_ID | Chr | Physical Position | CGEMS p-value | CGEMS Rank | 100K SNP | Physical Position | GEE p-value | FBAT p-value | MAF | Nearest Gene |
Minor Allele Frequency ≥10%
| ||||||||||
rs3017183 | 18 | 51,319,241 | 0.00024100 | 85 | rs3794889 | 51,212,935 | 0.017 | 0.799 | 0.224 |
TCF4
|
rs3017183 | 18 | 51,319,241 | 0.00024100 | 85 | rs4801149 | 51,214,227 | 0.044 | 0.983 | 0.221 |
TCF4
|
rs2253319 | 21 | 35,109,916 | 0.00041100 | 137 | rs2834645 | 35,109,556 | 0.009 | 0.293 | 0.206 |
RUNX1
|
rs392715 | 16 | 24,023,323 | 0.00041800 | 141 | rs10492797 | 24,122,453 | 0.036 | 0.407 | 0.175 |
PRKCB1
|
rs10256504 | 7 | 3,516,796 | 0.00092200 | 295 | rs4418248 | 3,194,181 | 1.8 × 10-4 | 0.056 | 0.109 |
SDK1
|
rs6102912 | 20 | 40,636,349 | 0.00111000 | 350 | rs986831 | 40,594,892 | 0.009 | 0.094 | 0.407 |
PTPRT
|
rs4782742 | 16 | 81,573,151 | 0.00127400 | 395 | rs254315 | 82,313,913 | 7.1 × 10-4 | 0.011 | 0.141 |
CDH13
|
rs2371438 | 2 | 212,791,037 | 0.00128500 | 401 | rs10497958 | 212,771,465 | 0.055 | 0.047 | 0.164 |
ERBB4
|
rs6577648 | 8 | 135,555,688 | 0.00144900 | 445 | rs10505624 | 135,607,862 | 4.9 × 10-4 | 0.007 | 0.147 |
ZFAT1
|
rs9327886 | 5 | 102,931,646 | 0.00154600 | 468 | rs10515347 | 102,950,833 | 0.006 | 0.062 | 0.354 |
NUDT12
|
rs6555491 | 5 | 7,799,792 | 0.00158700 | 478 | rs10512920 | 7,455,561 | 0.009 | 0.647 | 0.244 |
ADCY2
|
Minor Allele Frequency <10%
| ||||||||||
rs38276 | 7 | 14,078,240 | 0.00055700 | 181 | rs10486031 | 14,258,703 | 1.7 × 10-5 | 0.759 | 0.032 |
DGKB
|
rs216666 | 2 | 80,745,015 | 0.00057000 | 184 | rs10520247 | 79,693,452 | 2.8 × 10-5 | 0.240 | 0.065 |
CTNNA2
|
rs216666 | 2 | 80,745,015 | 0.00057000 | 184 | rs10520246 | 79,693,324 | 1.5 × 10-4 | 0.198 | 0.050 |
CTNNA2
|
rs1261256 | 5 | 22,490,853 | 0.00060200 | 193 | rs10520880 | 22,634,003 | 8.5 × 10-5 | 0.356 | 0.065 |
CDH12
|
rs7610584 | 3 | 171,635,885 | 0.00061900 | 196 | rs10513681 | 171,624,010 | 7.8 × 10-7 | 0.402 | 0.025 |
CLDN11
|
rs7329659 | 13 | 97,872,564 | 0.00064700 | 209 | rs7989050 | 97,680,299 | 6.0 × 10-6 | 0.258 | 0.014 |
FARP1
|
rs208354 | 7 | 2,554,104 | 0.00065000 | 211 | rs10487577 | 2,583,719 | 2.0 × 10-7 | N/A | 0.012 |
GNA12
|
rs3751832 | 16 | 77,771,773 | 0.00079900 | 257 | rs10514443 | 77,353,386 | 9.3 × 10-4 | N/A | 0.008 |
WWOX
|