After quality control (QC), this study included whole-genome sequencing (WGS) data for 1,439 colorectal cancer (CRC) cases and 720 controls from 5 studies, and GWAS array data for 58,131 CRC or advanced adenoma cases (3,674; 6.3% of cases) and 67,347 controls from 45 studies from GECCO, CORECT, and CCFR. The Stage 1 meta-analysis comprised existing genotyping data from 30 studies that were included in previously published CRC GWAS13 (link),18 (link),22 (link). After QC, the Stage 1 meta-analysis included 34,869 cases and 29,051 controls. Study participants were predominantly of European ancestry (31,843 cases and 26,783 controls; 91.7% of participants). Because it was shown previously that the vast majority of known CRC risk variants are shared between Europeans and East Asians17 (link), we included 3,026 cases and 2,268 controls of East Asian ancestry to increase power for discovery. The Stage 2 meta-analysis comprised newly generated genotype data involving 4 genotyping projects and 22 studies. After QC, the Stage 2 meta-analysis included 23,262 cases and 38,296 controls, all of European ancestry. Studies, sample selection, and matching are described in the Supplementary Text. Supplementary Table 1 provides details on sample numbers, and demographic characteristics of study participants. All participants provided written informed consent, and each study was approved by the relevant research ethics committee or institutional review board. Four normal colon mucosa biopsies for ATAC-seq were obtained from patients with a normal colon at colonoscopy at the Institut d’Investigació Biomèdica de Bellvitge (IDIBELL), Spain. Patients signed informed consent, and the protocol was approved by the Bellvitge Hospital Ethics Committee (Colscreen protocol PR084/16).