title: Use of a Novel Nonparametric Version of DEPTH to Identify Genomic Regions Associated with Prostate Cancer Risk.
abstract: 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.
  
  
  
  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.
  
  
  
  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.
  
  
  
  DEPTH can reveal new risk-associated regions that would not have been identified using a conventional logistic regression analysis of individual SNPs.
  
  
  
  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.
authors.affiliation: Cancer Epidemiology Centre, Cancer Council Victoria, Melbourne, Australia.|Centre for Epidemiology and Biostatistics, University of Melbourne, Melbourne, Australia.
authors.forename: Robert J
authors.initials: RJ
authors.lastname: MacInnis
authors.affiliation: Centre for Epidemiology and Biostatistics, University of Melbourne, Melbourne, Australia.
authors.forename: Daniel F
authors.initials: DF
authors.lastname: Schmidt
authors.affiliation: Centre for Epidemiology and Biostatistics, University of Melbourne, Melbourne, Australia.
authors.forename: Enes
authors.initials: E
authors.lastname: Makalic
authors.affiliation: Human Genetics Foundation, Torino, Italy.|Université Paris-Saclay, Univ. Paris-Sud, UVSQ, CESP, INSERM, Villejuif, France.|Gustave Roussy, F-94805, Villejuif, France.
authors.forename: Gianluca
authors.initials: G
authors.lastname: Severi
authors.affiliation: Menzies Institute for Medical Research, University of Tasmania, Hobart, Tasmania.
authors.forename: Liesel M
authors.initials: LM
authors.lastname: FitzGerald
authors.affiliation: IBM Research, Zurich, Switzerland.|UNU-MERIT (United Nations University - Maastricht Economic and Social Research Institute on Innovation and Technology), Maastricht University, Maastricht, the Netherlands.
authors.forename: Matthias
authors.initials: M
authors.lastname: Reumann
authors.affiliation: Centre for Epidemiology and Biostatistics, University of Melbourne, Melbourne, Australia.
authors.forename: Miroslaw K
authors.initials: MK
authors.lastname: Kapuscinski
authors.affiliation: Warsaw University of Technology, Warsaw, Poland.|School of Mathematics and Statistics, University of Melbourne, Parkville, Victoria, Australia.
authors.forename: Adam
authors.initials: A
authors.lastname: Kowalczyk
authors.affiliation: IBM Research - Australia, Carlton, Australia.
authors.forename: Zeyu
authors.initials: Z
authors.lastname: Zhou
authors.affiliation: IBM Research - Australia, Carlton, Australia.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Goudey
authors.affiliation: School of Mathematics and Statistics, University of Melbourne, Parkville, Victoria, Australia.
authors.forename: Guoqi
authors.initials: G
authors.lastname: Qian
authors.affiliation: Centre for Epidemiology and Biostatistics, University of Melbourne, Melbourne, Australia.
authors.forename: Quang M
authors.initials: QM
authors.lastname: Bui
authors.affiliation: Genetic Epidemiology Laboratory, Department of Pathology, University of Melbourne, Victoria, Australia.|Melbourne Bioinformatics Platform, Victorian Life Sciences Computation Initiative, University of Melbourne, Victoria, Australia.
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Park
authors.affiliation: Centre for Epidemiology and Biostatistics, University of Melbourne, Melbourne, Australia.
authors.forename: Adam
authors.initials: A
authors.lastname: Freeman
authors.affiliation: Genetic Epidemiology Laboratory, Department of Pathology, University of Melbourne, Victoria, Australia.
authors.forename: Melissa C
authors.initials: MC
authors.lastname: Southey
authors.affiliation: Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge, United Kingdom.
authors.forename: Ali Amin
authors.initials: AA
authors.lastname: Al Olama
authors.affiliation: The Institute of Cancer Research, London, United Kingdom.
authors.forename: Zsofia
authors.initials: Z
authors.lastname: Kote-Jarai
authors.forename: Rosalind A
authors.initials: RA
authors.lastname: Eeles
authors.affiliation: Centre for Epidemiology and Biostatistics, University of Melbourne, Melbourne, Australia. j.hopper@unimelb.edu.au.|Department of Epidemiology, School of Public Health and Institute of Health and Environment, Seoul National University, Seoul, South Korea.
authors.forename: John L
authors.initials: JL
authors.lastname: Hopper
authors.affiliation: Cancer Epidemiology Centre, Cancer Council Victoria, Melbourne, Australia.|Centre for Epidemiology and Biostatistics, University of Melbourne, Melbourne, Australia.
authors.forename: Graham G
authors.initials: GG
authors.lastname: Giles
mesh_terms: D001315:Australia; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study / Q000379:methods*; D006801:Humans; D000069550:Machine Learning; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011471:Prostatic Neoplasms / Q000235:genetics*; D006113:United Kingdom