Table 1 Significant colorectal cancer genes detected by PWAS
Symbol | Name | Chrom | Most significant variant in the region | Most significant protein affecting variant | Generalized PWAS q value | Dominant PWAS q value | Dominant PWAS Cohen’s d | Recessive PWAS q value | Recessive PWAS Cohen’s d | Literature evidence |
|---|---|---|---|---|---|---|---|---|---|---|
MUTYH | mutY DNA glycosylase | 1 | rs12139364 | rs36053993 | 2.3E−6 (***) | 0.34 | n.s. | 1.2E−4 (***) | − 0.079 | Strong, biallelic mutations increase colorectal cancer risk by a factor of 17–44 [23] |
p = 6.3E−4 | p = 1.2E−3 | |||||||||
FHL3 | Four and a half LIM domains 3 | 1 | rs147339918 | rs145496383 | 0.01 (*) | 0.92 | n.s. | 0.024 (*) | − 0.037 | Moderate, acts as tumor suppressor in breast and other cancer types [24] |
p = 1.5E−3 | p = 0.016 | |||||||||
OSTC | Oligosaccharyltransferase complex non-catalytic subunit | 4 | rs17038839 | rs202168879 | 0.01 (*) | 0.96 | n.s. | 0.024 (*) | 0.026 | Weak, subunit of the OST complex which has been associated with lung and ovarian cancer [25, 26] |
p = 9.1E−4 | p = 0.016 | |||||||||
CDK2AP2/DOC-1R | Cyclin-dependent kinase 2-associated protein 2 | 11 | rs147242558 | rs530762126 | 0.024 (*) | 1 | n.s. | 7.8E−3 (*) | − 5.4E−3 | Strong, inhibits CDK2 and G1/S phase transition, a paralog of p14 and CDK2AP1, binds CDK2AP1 [27, 28] |
p = 2.7E−3 | p = 0.4 | |||||||||
POU5F1B/BRN4 | POU class 5 homeobox 1B | 8 | *rs6983267 | *rs6998061 | 0.027 (*) | 0.02 (*) | 0.09 | 1 | n.s. | Strong, promotes proliferation in several cancer types, GWAS hit in colorectal cancer [29,30,31] |
p = 5.9E−9 | p = 1.4E−7 | |||||||||
CCDC172 | Coiled-coil domain containing 172 | 10 | rs200485970 | rs532636333 | 0.035 (*) | 0.96 | n.s. | 0.059 | n.s. | None |
p = 1.6E−4 | p = 0.055 |