Metastasis to distal organ is the major cause of cancer death. The underlying germline genetic factors for colorectal cancer (CRC) metastasis are currently unclear. This study identifies metastasis-relevant genes and pathways via a combinatorial strategy of genome-wide association study (GWAS) of clinically defined 1282 metastasis-positive vs 1395 metastasis-negative cases, in silico functional annotation and pathway analysis, followed by expression validation of candidate genes in overall and gender-, stage- and distal-organ specific CRC subtypes.  Validated metastasis-relevant genes can serve as features for developing sub-type specific signatures to better manage metastasis-prone stage I-III CRC patients instead of the current one-size-fits-all approach. (By Dr Peh Yean Cheah, https://jmg.bmj.com/content/61/3/276 )