American Association for Cancer Research
epi-22-1209_figure_s1_suppsf1.pdf (128.46 kB)

Figure S1 from Using DEPendency of Association on the Number of Top Hits (DEPTH) as a Complementary Tool to Identify Novel Colorectal Cancer Susceptibility Loci

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journal contribution
posted on 2023-09-01, 08:40 authored by John Lai, Chi Kuen Wong, Daniel F. Schmidt, Miroslaw K. Kapuscinski, Karen Alpen, Robert J. MacInnis, Daniel D. Buchanan, Aung K. Win, Jane C. Figueiredo, Andrew T. Chan, Tabitha A. Harrison, Michael Hoffmeister, Emily White, Loic Le Marchand, Rish K. Pai, Ulrike Peters, John L. Hopper, Mark A. Jenkins, Enes Makalic

Supplementary Figure S1 showing the flow chart of the analyses for identifying novel, unique, and common risk regions from DEPTH and logistic regression analyses.


National Institutes of Health (NIH)

Deutsche Forschungsgemeinschaft (DFG)

Nationales Centrum für Tumorerkrankungen Heidelberg (NCT Heidelberg)



DEPendency of association on the number of Top Hits (DEPTH) is an approach to identify candidate susceptibility regions by considering the risk signals from overlapping groups of sequential variants across the genome. We applied a DEPTH analysis using a sliding window of 200 SNPs to colorectal cancer data from the Colon Cancer Family Registry (CCFR; 5,735 cases and 3,688 controls), and Genetics and Epidemiology of Colorectal Cancer Consortium (GECCO; 8,865 cases and 10,285 controls) studies. A DEPTH score > 1 was used to identify candidate susceptibility regions common to both analyses. We compared DEPTH results against those from conventional genome-wide association study (GWAS) analyses of these two studies as well as against 132 published susceptibility regions. Initial DEPTH analysis revealed 2,622 (CCFR) and 3,686 (GECCO) candidate susceptibility regions, of which 569 were common to both studies. Bootstrapping revealed 40 and 49 candidate susceptibility regions in the CCFR and GECCO data sets, respectively. Notably, DEPTH identified at least 82 regions that would not be detected using conventional GWAS methods, nor had they been identified by previous colorectal cancer GWASs. We found four reproducible candidate susceptibility regions (2q22.2, 2q33.1, 6p21.32, 13q14.3). The highest DEPTH scores were in the human leukocyte antigen locus at 6p21 where the strongest associated SNPs were rs762216297, rs149490268, rs114741460, and rs199707618 for the CCFR data, and rs9270761 for the GECCO data. DEPTH can identify candidate susceptibility regions for colorectal cancer not identified using conventional analyses of larger datasets. DEPTH has potential as a powerful complementary tool to conventional GWAS analyses for discovering susceptibility regions within the genome.

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