title: Reducing GWAS Complexity.
abstract: Genome-wide association studies (GWAS) have revealed numerous genomic 'hits' associated with complex phenotypes. In most cases these hits, along with surrogate genetic variation as measure by numerous single nucleotide polymorphisms (SNPs) that are in linkage disequilibrium, are not in coding genes making assignment of functionality or causality intractable. Here we propose that fine-mapping along with the matching of risk SNPs at chromatin biofeatures lessen this complexity by reducing the number of candidate functional/causal SNPs. For example, we show here that only on average 2 SNPs per prostate cancer risk locus are likely candidates for functionality/causality; we further propose that this manageable number should be taken forward in mechanistic studies. The candidate SNPs can be looked up for each prostate cancer risk region in 2 recent publications in 2015 (1,2) from our groups.
authors.affiliation: a Bioinformatics and Computational Biology Research Center, Biomedical Sciences, Cedars-Sinai Medical Center , Los Angeles , CA , USA.
authors.forename: Dennis J
authors.initials: DJ
authors.lastname: Hazelett
authors.affiliation: b Departments of Preventive Medicine and Urology , USC/Norris Cancer Center , USA.
authors.forename: David V
authors.initials: DV
authors.lastname: Conti
authors.affiliation: b Departments of Preventive Medicine and Urology , USC/Norris Cancer Center , USA.
authors.forename: Ying
authors.initials: Y
authors.lastname: Han
authors.affiliation: c Division of Genetics & Epidemiology, Centre of Cancer Genetic Epidemiology, University of Cambridge , Cambridge , UK.
authors.forename: Ali Amin
authors.initials: AA
authors.lastname: Al Olama
authors.affiliation: c Division of Genetics & Epidemiology, Centre of Cancer Genetic Epidemiology, University of Cambridge , Cambridge , UK.
authors.forename: Doug
authors.initials: D
authors.lastname: Easton
authors.affiliation: d The Institute of Cancer Research & Royal Marsden NHS Foundation Trust , London , UK.
authors.forename: Rosalind A
authors.initials: RA
authors.lastname: Eeles
authors.affiliation: d The Institute of Cancer Research & Royal Marsden NHS Foundation Trust , London , UK.
authors.forename: Zsofia
authors.initials: Z
authors.lastname: Kote-Jarai
authors.affiliation: b Departments of Preventive Medicine and Urology , USC/Norris Cancer Center , USA.
authors.forename: Christopher A
authors.initials: CA
authors.lastname: Haiman
authors.affiliation: b Departments of Preventive Medicine and Urology , USC/Norris Cancer Center , USA.|d The Institute of Cancer Research & Royal Marsden NHS Foundation Trust , London , UK.
authors.forename: Gerhard A
authors.initials: GA
authors.lastname: Coetzee
mesh_terms: D000818:Animals; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D015894:Genome, Human / Q000235:genetics*; D055106:Genome-Wide Association Study / Q000379:methods* / Q000639:trends; D006801:Humans; D015810:Linkage Disequilibrium / Q000502:physiology*; D020641:Polymorphism, Single Nucleotide / Q000502:physiology
keywords: Cancer; GWAS; SNP; chromatin; enhancer; fine-mapping; non-coding DNA