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Use of a Novel Nonparametric Version of DEPTH to Identify Genomic Regions Associated with Prostate Cancer Risk.

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Date
2016-12
ICR Author
Eeles, Rosalind
Kote-Jarai, Zsofia
Author
MacInnis, RJ
Schmidt, DF
Makalic, E
Severi, G
FitzGerald, LM
Reumann, M
Kapuscinski, MK
Kowalczyk, A
Zhou, Z
Goudey, B
Qian, G
Bui, QM
Park, DJ
Freeman, A
Southey, MC
Al Olama, AA
Kote-Jarai, Z
Eeles, RA
Hopper, JL
Giles, GG
UK Genetic Prostate Cancer Study Collaborators
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Type
Journal Article
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Abstract
Background We have developed a genome-wide association study analysis method called DEPTH (DEPendency of association on the number of Top Hits) to identify genomic regions potentially associated with disease by considering overlapping groups of contiguous markers (e.g., SNPs) across the genome. DEPTH is a machine learning algorithm for feature ranking of ultra-high dimensional datasets, built from well-established statistical tools such as bootstrapping, penalized regression, and decision trees. Unlike marginal regression, which considers each SNP individually, the key idea behind DEPTH is to rank groups of SNPs in terms of their joint strength of association with the outcome. Our aim was to compare the performance of DEPTH with that of standard logistic regression analysis.Methods We selected 1,854 prostate cancer cases and 1,894 controls from the UK for whom 541,129 SNPs were measured using the Illumina Infinium HumanHap550 array. Confirmation was sought using 4,152 cases and 2,874 controls, ascertained from the UK and Australia, for whom 211,155 SNPs were measured using the iCOGS Illumina Infinium array.Results From the DEPTH analysis, we identified 14 regions associated with prostate cancer risk that had been reported previously, five of which would not have been identified by conventional logistic regression. We also identified 112 novel putative susceptibility regions.Conclusions DEPTH can reveal new risk-associated regions that would not have been identified using a conventional logistic regression analysis of individual SNPs.Impact This study demonstrates that the DEPTH algorithm could identify additional genetic susceptibility regions that merit further investigation. Cancer Epidemiol Biomarkers Prev; 25(12); 1619-24. ©2016 AACR.
URI
https://repository.icr.ac.uk/handle/internal/959
DOI
https://doi.org/10.1158/1055-9965.epi-16-0301
Collections
  • Genetics and Epidemiology
  • Radiotherapy and Imaging
Subject
UK Genetic Prostate Cancer Study Collaborators
Humans
Prostatic Neoplasms
Genetic Predisposition to Disease
Polymorphism, Single Nucleotide
Middle Aged
Australia
Male
Genome-Wide Association Study
Machine Learning
United Kingdom
Research team
Oncogenetics
Language
eng
Date accepted
2016-08-04
License start date
2016-12
Citation
Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology, 2016, 25 (12), pp. 1619 - 1624

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