title: A systematic review of cancer GWAS and candidate gene meta-analyses reveals limited overlap but similar effect sizes.
abstract: Candidate gene and genome-wide association studies (GWAS) represent two complementary approaches to uncovering genetic contributions to common diseases. We systematically reviewed the contributions of these approaches to our knowledge of genetic associations with cancer risk by analyzing the data in the Cancer Genome-wide Association and Meta Analyses database (Cancer GAMAdb). The database catalogs studies published since January 1, 2000, by study and cancer type. In all, we found that meta-analyses and pooled analyses of candidate genes reported 349 statistically significant associations and GWAS reported 269, for a total of 577 unique associations. Only 41 (7.1%) associations were reported in both candidate gene meta-analyses and GWAS, usually with similar effect sizes. When considering only noteworthy associations (defined as those with false-positive report probabilities≤0.2) and accounting for indirect overlap, we found 202 associations, with 27 of those appearing in both meta-analyses and GWAS. Our findings suggest that meta-analyses of well-conducted candidate gene studies may continue to add to our understanding of the genetic associations in the post-GWAS era.
authors.affiliation: Division of Cancer Control and Population Sciences, National Cancer Institute, Bethesda, Maryland, USA.
authors.forename: Christine Q
authors.initials: CQ
authors.lastname: Chang
authors.affiliation: Centers for Disease Control and Prevention, Atlanta, Georgia, USA.
authors.forename: Ajay
authors.initials: A
authors.lastname: Yesupriya
authors.affiliation: Department of Epidemiology, Rollins School of Public Health, Emory University, Atlanta, Georgia, USA.
authors.forename: Jessica L
authors.initials: JL
authors.lastname: Rowell
authors.affiliation: University of Massachusetts Medical School, Graduate School of Biomedical Sciences, Clinical and Population Health Research Program, Worcester, Massachusetts, USA.
authors.forename: Camilla B
authors.initials: CB
authors.lastname: Pimentel
authors.affiliation: University of Massachusetts Medical School, Graduate School of Biomedical Sciences, Clinical and Population Health Research Program, Worcester, Massachusetts, USA.
authors.forename: Melinda
authors.initials: M
authors.lastname: Clyne
authors.affiliation: McKing Consulting Corporation, Atlanta, Georgia, USA.
authors.forename: Marta
authors.initials: M
authors.lastname: Gwinn
authors.affiliation: 1] Division of Cancer Control and Population Sciences, National Cancer Institute, Bethesda, Maryland, USA [2] Office of Public Health Genomics, Centers for Disease Control and Prevention, Atlanta, Georgia, USA.
authors.forename: Muin J
authors.initials: MJ
authors.lastname: Khoury
authors.affiliation: Office of Public Health Genomics, Centers for Disease Control and Prevention, Atlanta, Georgia, USA.
authors.forename: Anja
authors.initials: A
authors.lastname: Wulf
authors.affiliation: Division of Cancer Control and Population Sciences, National Cancer Institute, Bethesda, Maryland, USA.
authors.forename: Sheri D
authors.initials: SD
authors.lastname: Schully
mesh_terms: D016022:Case-Control Studies; D055106:Genome-Wide Association Study; D006801:Humans; D009369:Neoplasms / Q000235:genetics*