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@ARTICLE{Lai:277120,
author = {J. Lai and C. K. Wong and D. F. Schmidt and M. K.
Kapuscinski and K. Alpen and R. J. Maclnnis and D. D.
Buchanan and A. K. Win and J. C. Figueiredo and A. T. Chan
and T. A. Harrison and M. Hoffmeister$^*$ and E. White and
L. Le Marchand and R. K. Pai and U. Peters and J. L. Hopper
and M. A. Jenkins and E. Makalic},
title = {{U}sing {DEP}endency of association on the number of {T}op
{H}its ({DEPTH}) as a complementary tool to identify novel
colorectal cancer susceptibility loci.},
journal = {Cancer epidemiology, biomarkers $\&$ prevention},
volume = {32},
number = {9},
issn = {1055-9965},
address = {Philadelphia, Pa.},
publisher = {AACR},
reportid = {DKFZ-2023-01285},
pages = {1153-1159},
year = {2023},
note = {2023 Sep 1;32(9):1153-1159},
abstract = {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 conducted a DEPTH
analysis using a sliding window of 200 SNPs to colorectal
cancer (CRC) data from the Colon Cancer Family Registry
(CCFR) (5,735 cases and 3,688 controls), and GECCO (8,865
cases and 10,285 controls) studies. A DEPTH score >1 was
used to identify candidate susceptibility regions common to
both studies. We compared DEPTH results against those from
conventional 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 CRC GWASs. We found
four reproducible candidate susceptibility regions (2q22.2,
2q33.1, 6p21.32, 13q14.3). The highest DEPTH scores were in
the HLA 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 CRC 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.},
cin = {C070},
ddc = {610},
cid = {I:(DE-He78)C070-20160331},
pnm = {313 - Krebsrisikofaktoren und Prävention (POF4-313)},
pid = {G:(DE-HGF)POF4-313},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:37364297},
doi = {10.1158/1055-9965.EPI-22-1209},
url = {https://inrepo02.dkfz.de/record/277120},
}