Table 1.
Two-stage multiple Cox regressions of genome-wide SNPs associated with CRP predicting colorectal cancer risk
| SNP | Chr | Position¥ | Gene | Allele | Stage 1 | Stage 2 | |||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Adjustment for age and 10 PCs | Adjustment for covariates* | ||||||||||||
| in addition to age and 10 PCs | |||||||||||||
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| Ref | Alt | HR | (95% CI) | p | p-het† | HR | (95% CI) | p | p-het† | ||||
| GWAS examining CRP as a binary outcome reflecting high immune response and chronic inflammation (CRP > 3.0 mg/L) | |||||||||||||
| rs2794520 | 1 | 159678816 | CRPP1/CRP | C | T | 0.97 | (0.87-1.08) | 0.555 | 0.271 | 0.95 | (0.86-1.06) | 0.361 | 0.563 |
| rs2243458 | 12 | 121424490 | HNF1A | C | T | 1.02 | (0.91-1.13) | 0.792 | 0.047 | 1.06 | (0.95-1.19) | 0.276 | 0.047 |
| rs1169311 | 12 | 121440731 | C12orf43 | C | T | 1.02 | (0.91-1.13) | 0.775 | 0.168 | 1.05 | (0.94-1.17) | 0.398 | 0.098 |
| rs429358 | 19 | 45411941 | APOE | T | C | 0.95 | (0.80-1.13) | 0.554 | 0.745 | 0.95 | (0.80-1.13) | 0.568 | 0.511 |
| rs5117 | 19 | 45418790 | APOC1 | T | C | 1.02 | (0.72-1.45) | 0.893 | 0.216 | 1.05 | (0.74-1.49) | 0.793 | 0.157 |
| GWASs analyzing CRP as a continuous variable that was naturally log-transformed (mg/L) | |||||||||||||
| rs75460349 | 1 | 27180088 | ZDHHC18 | C | A | 1.16 | (0.78-1.73) | 0.459 | 0.970 | 1.16 | (0.78-1.74) | 0.469 | 0.877 |
| rs2293476 | 1 | 40036847 | PABPC4 | G | C | 1.04 | (0.92-1.18) | 0.525 | 0.954 | 1.05 | (0.92-1.19) | 0.490 | 0.904 |
| rs1805096 | 1 | 66102257 | LEPR | A | G | 1.03 | (0.92-1.15) | 0.608 | 0.298 | 1.03 | (0.92-1.15) | 0.619 | 0.376 |
| rs469772 | 1 | 91530305 | ZNF644 | T | C | 1.12 | (0.99-1.28) | 0.081 | 0.239 | 1.08 | (0.95-1.23) | 0.257 | 0.257 |
| rs4129267 | 1 | 154426264 | IL6R | T | C | 0.92 | (0.83-1.02) | 0.122 | 0.467 | 0.90 | (0.81-1.00) | 0.051 | 0.587 |
| rs2794520 | 1 | 159678816 | CRPP1/CRP | T | C | 1.03 | (0.93-1.15) | 0.555 | 0.271 | 1.05 | (0.95-1.17) | 0.361 | 0.563 |
| rs1800947 | 1 | 159683438 | CRP | G | C | 1.30 | (0.88-1.92) | 0.180 | 0.422 | 1.37 | (0.92-2.05) | 0.125 | 0.401 |
| rs1417938 | 1 | 159684186 | CRP | T | C | 1.02 | (0.91-1.14) | 0.694 | 0.576 | 1.03 | (0.92-1.15) | 0.657 | 0.539 |
| rs10925027 | 1 | 247612562 | NLRP3 | C | T | 1.15 | (0.97-1.36) | 0.117 | 0.725 | 1.21 | (1.01-1.46) | 0.043 | 0.576 |
| rs12995480 | 2 | 629881 | TMEM18 | T | C | 1.07 | (0.94-1.22) | 0.328 | 0.897 | 1.01 | (0.88-1.16) | 0.888 | 0.969 |
| rs1260326 | 2 | 27730940 | GCKR | C | T | 0.97 | (0.87-1.09) | 0.636 | 0.785 | 1.00 | (0.89-1.12) | 0.999 | 0.765 |
| rs4246598 | 2 | 88438050 | FABP1 | C | A | 0.97 | (0.87-1.07) | 0.529 | 0.526 | 0.98 | (0.88-1.09) | 0.757 | 0.597 |
| rs9284725 | 2 | 102744854 | IL1R1 | A | C | 1.04 | (0.92-1.18) | 0.525 | 0.778 | 1.04 | (0.91-1.18) | 0.576 | 0.779 |
| rs13409371 | 2 | 113838145 | IL1F10 | G | A | 1.03 | (0.93-1.15) | 0.559 | 0.834 | 1.02 | (0.92-1.14) | 0.691 | 0.782 |
| rs1441169 | 2 | 214033530 | IKZF2 | G | A | 1.05 | (0.95-1.16) | 0.363 | 0.399 | 1.07 | (0.96-1.19) | 0.215 | 0.741 |
| rs2352975 | 3 | 49891885 | TRAIP | T | C | 1.16 | (0.95-1.41) | 0.144 | 0.842 | 1.17 | (0.95-1.43) | 0.130 | 0.966 |
| rs1514895 | 3 | 170705693 | EIF5A2 | A | G | 1.06 | (0.94-1.18) | 0.354 | 0.934 | 1.08 | (0.96-1.21) | 0.212 | 0.934 |
| rs4705952 | 5 | 131839618 | IRF1 | A | G | 1.07 | (0.93-1.23) | 0.335 | 0.216 | 1.03 | (0.89-1.18) | 0.709 | 0.083 |
| rs17658229 | 5 | 172191052 | DUSP1 | T | C | 0.97 | (0.72-1.32) | 0.868 | 0.055 | 0.93 | (0.68-1.27) | 0.652 | 0.166 |
| rs9271608 | 6 | 32591588 | HLA-DQA1 | A | G | 1.13 | (0.71-1.80) | 0.606 | 0.699 | 1.20 | (0.74-1.94) | 0.453 | 0.567 |
| rs12202641 | 6 | 116314634 | FRK | T | C | 0.91 | (0.82-1.01) | 0.087 | 0.167 | 0.90 | (0.80-1.00) | 0.050 | 0.124 |
| rs6901250 | 6 | 117114025 | GPRC6A | G | A | 1.02 | (0.91-1.15) | 0.679 | 0.716 | 1.06 | (0.95-1.20) | 0.292 | 0.656 |
| rs1490384 | 6 | 126851160 | CENPW | T | C | 0.94 | (0.85-1.05) | 0.295 | 0.507 | 0.96 | (0.86-1.07) | 0.420 | 0.596 |
| rs9385532 | 6 | 130371227 | L3MBTL3 | T | C | 0.96 | (0.86-1.07) | 0.485 | 0.614 | 1.00 | (0.90-1.12) | 0.974 | 0.860 |
| rs1880241 | 7 | 22759469 | IL6 | G | A | 0.94 | (0.85-1.04) | 0.234 | 0.016 | 0.99 | (0.89-1.10) | 0.830 | 0.013 |
| rs2710804 | 7 | 36084529 | EEPD1 | T | C | 0.93 | (0.83-1.04) | 0.184 | 0.468 | 0.93 | (0.83-1.04) | 0.194 | 0.279 |
| rs13233571 | 7 | 72971231 | BCL7B | T | C | 1.01 | (0.87-1.19) | 0.857 | 1.000 | 0.94 | (0.80-1.11) | 0.478 | 0.993 |
| rs4841132 | 8 | 9183596 | PPP1R3B | A | G | 0.85 | (0.70-1.03) | 0.098 | 0.824 | 0.88 | (0.72-1.06) | 0.175 | 0.598 |
| rs2064009 | 8 | 117007850 | TRPS1 | C | T | 0.96 | (0.86-1.07) | 0.444 | 0.550 | 0.95 | (0.85-1.05) | 0.317 | 0.526 |
| rs2891677 | 8 | 126344208 | NSMCE2 | C | T | 1.00 | (0.90-1.11) | 0.975 | 0.843 | 1.03 | (0.93-1.14) | 0.582 | 0.992 |
| rs643434 | 9 | 136142355 | ABO | G | A | 0.93 | (0.84-1.04) | 0.201 | 0.541 | 0.96 | (0.86-1.07) | 0.449 | 0.489 |
| rs1051338 | 10 | 91007360 | LIPA | T | G | 1.02 | (0.90-1.14) | 0.802 | 0.581 | 1.02 | (0.91-1.15) | 0.731 | 0.452 |
| rs10832027 | 11 | 13357183 | ARNTL | G | A | 0.96 | (0.85-1.07) | 0.427 | 0.540 | 0.95 | (0.85-1.07) | 0.416 | 0.835 |
| rs10838687 | 11 | 47312892 | MADD | G | T | 0.99 | (0.87-1.13) | 0.894 | 0.811 | 0.98 | (0.86-1.12) | 0.807 | 0.891 |
| rs1582763 | 11 | 60021948 | MS4A4A | A | G | 1.04 | (0.93-1.16) | 0.490 | 0.952 | 1.00 | (0.89-1.11) | 0.955 | 0.955 |
| rs7121935 | 11 | 72496148 | STARD10 | A | G | 0.99 | (0.88-1.11) | 0.836 | 0.330 | 1.02 | (0.90-1.14) | 0.803 | 0.184 |
| rs11108056 | 12 | 95855385 | METAP2 | G | C | 0.99 | (0.83-1.19) | 0.951 | 0.131 | 1.02 | (0.84-1.23) | 0.842 | 0.199 |
| rs10778215 | 12 | 103537266 | C12orf42 | A | T | 0.96 | (0.87-1.06) | 0.430 | 0.922 | 0.99 | (0.90-1.10) | 0.904 | 0.740 |
| rs7310409 | 12 | 121424861 | HNF1A | A | G | 0.99 | (0.89-1.11) | 0.910 | 0.159 | 0.98 | (0.88-1.09) | 0.653 | 0.103 |
| rs2239222 | 14 | 73011885 | RGS6 | A | G | 1.03 | (0.91-1.18) | 0.603 | 0.835 | 1.05 | (0.92-1.19) | 0.476 | 0.526 |
| rs112635299 | 14 | 94838142 | SERPINA1/SERPINA2P | T | G | 0.88 | (0.57-1.36) | 0.570 | 0.199 | 0.95 | (0.62-1.48) | 0.828 | 0.364 |
| rs4774590 | 15 | 51745277 | DMXL2 | A | G | 1.17 | (1.05-1.30) | 0.004 | 0.139 | 1.17 | (1.05-1.30) | 0.004 | 0.229 |
| rs1189402 | 15 | 53728154 | WDR72 | G | A | 0.93 | (0.83-1.05) | 0.241 | 0.831 | 0.95 | (0.84-1.07) | 0.372 | 0.822 |
| rs340005 | 15 | 60878030 | RORA | G | A | 1.02 | (0.92-1.14) | 0.703 | 0.342 | 0.96 | (0.86-1.07) | 0.464 | 0.634 |
| rs10521222 | 16 | 51158710 | SALL1 | T | C | 1.41 | (0.86-2.30) | 0.172 | 0.510 | 1.16 | (0.68-1.98) | 0.587 | 0.559 |
| rs1558902 | 16 | 53803574 | FTO | T | A | 1.01 | (0.91-1.13) | 0.834 | 0.791 | 1.02 | (0.91-1.14) | 0.732 | 0.851 |
| rs178810 | 17 | 16097430 | NCOR1 | C | T | 0.95 | (0.86-1.06) | 0.388 | 0.457 | 0.97 | (0.87-1.08) | 0.546 | 0.357 |
| rs10512597 | 17 | 72699833 | CD300LF/RAB37 | T | C | 0.95 | (0.82-1.09) | 0.443 | 0.097 | 0.97 | (0.84-1.12) | 0.682 | 0.142 |
| rs2852151 | 18 | 12841176 | PTPN2 | G | A | 0.96 | (0.87-1.07) | 0.491 | 0.276 | 0.95 | (0.85-1.06) | 0.358 | 0.430 |
| rs4092465 | 18 | 55080437 | ONECUT2 | A | G | 0.95 | (0.75-1.19) | 0.646 | 0.915 | 0.93 | (0.74-1.18) | 0.564 | 0.957 |
| rs12960928 | 18 | 57897803 | MC4R | T | C | 0.99 | (0.88-1.12) | 0.915 | 0.814 | 0.99 | (0.88-1.11) | 0.818 | 0.875 |
| rs4420638 | 19 | 45422946 | APOC1 | G | A | 1.03 | (0.70-1.50) | 0.892 | 0.766 | 0.93 | (0.63-1.38) | 0.731 | 0.669 |
| rs1800961 | 20 | 43042364 | HNF4A | T | C | 0.90 | (0.53-1.52) | 0.687 | 0.372 | 0.89 | (0.51-1.55) | 0.681 | 0.392 |
| rs2315008 | 20 | 62343956 | ZGPAT | T | G | 1.08 | (0.96-1.20) | 0.195 | 0.620 | 1.10 | (0.98-1.22) | 0.096 | 0.961 |
| rs2836878 | 21 | 40465534 | PSMG1 | A | G | 1.11 | (0.99-1.24) | 0.078 | 0.288 | 1.11 | (0.99-1.24) | 0.080 | 0.319 |
| rs6001193 | 22 | 39074737 | TOMM22 | G | A | 1.01 | (0.91-1.13) | 0.846 | 0.320 | 1.04 | (0.93-1.17) | 0.445 | 0.606 |
Alt, alternative; Chr, chromosome; CI, confidence interval; CRP, C-reactive protein; GWAS, genome-wide association study; HR, hazard ratio; PCs, principal components; Ref, reference; SFA, saturated fatty acids; SNP, single-nucleotide polymorphism; WHI, Women’s Health Initiative studies.
*
Covariates adjusted in the analyses include education; annual family income; family history of colorectal cancer; cardiovascular disease ever; high cholesterol requiring medication ever; body mass index; waist-to-hip ratio; physical activity; % calories from SFA/day; dietary alcohol in g/day; number of cigarettes/day; age at menopause; duration of oral contraceptive use; and durations of exogenous estrogen (E)-only and E plus progestin use.
¥
GRCh 37 coordinated.
†
Heterogeneity in estimates among the 5 WHI sub-GWASs was evaluated by Cochran’s Q test with fixed effects.