title: Genome-wide association studies, field synopses, and the development of the knowledge base on genetic variation and human diseases.
abstract: Genome-wide association studies (GWAS) have led to a rapid increase in available data on common genetic variants and phenotypes and numerous discoveries of new loci associated with susceptibility to common complex diseases. Integrating the evidence from GWAS and candidate gene studies depends on concerted efforts in data production, online publication, database development, and continuously updated data synthesis. Here the authors summarize current experience and challenges on these fronts, which were discussed at a 2008 multidisciplinary workshop sponsored by the Human Genome Epidemiology Network. Comprehensive field synopses that integrate many reported gene-disease associations have been systematically developed for several fields, including Alzheimer's disease, schizophrenia, bladder cancer, coronary heart disease, preterm birth, and DNA repair genes in various cancers. The authors summarize insights from these field synopses and discuss remaining unresolved issues -- especially in the light of evidence from GWAS, for which they summarize empirical P-value and effect-size data on 223 discovered associations for binary outcomes (142 with P < 10(-7)). They also present a vision of collaboration that builds reliable cumulative evidence for genetic associations with common complex diseases and a transparent, distributed, authoritative knowledge base on genetic variation and human health. As a next step in the evolution of Human Genome Epidemiology reviews, the authors invite investigators to submit field synopses for possible publication in the American Journal of Epidemiology.
authors.affiliation: Office of Public Health Genomics, National Center for Chronic Disease Prevention and Health Promotion, Centers for Disease Control and Prevention, Atlanta, GA 30341, USA. mukl@cdc.gov
authors.forename: Muin J
authors.initials: MJ
authors.lastname: Khoury
authors.forename: Lars
authors.initials: L
authors.lastname: Bertram
authors.forename: Paolo
authors.initials: P
authors.lastname: Boffetta
authors.forename: Adam S
authors.initials: AS
authors.lastname: Butterworth
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Chanock
authors.forename: Siobhan M
authors.initials: SM
authors.lastname: Dolan
authors.forename: Isabel
authors.initials: I
authors.lastname: Fortier
authors.forename: Montserrat
authors.initials: M
authors.lastname: Garcia-Closas
authors.forename: Marta
authors.initials: M
authors.lastname: Gwinn
authors.forename: Julian P T
authors.initials: JP
authors.lastname: Higgins
authors.forename: A Cecile J W
authors.initials: AC
authors.lastname: Janssens
authors.forename: James
authors.initials: J
authors.lastname: Ostell
authors.forename: Ryan P
authors.initials: RP
authors.lastname: Owen
authors.forename: Roberta A
authors.initials: RA
authors.lastname: Pagon
authors.forename: Timothy R
authors.initials: TR
authors.lastname: Rebbeck
authors.forename: Nathaniel
authors.initials: N
authors.lastname: Rothman
authors.forename: Jonine L
authors.initials: JL
authors.lastname: Bernstein
authors.forename: Paul R
authors.initials: PR
authors.lastname: Burton
authors.forename: Harry
authors.initials: H
authors.lastname: Campbell
authors.forename: Anand
authors.initials: A
authors.lastname: Chockalingam
authors.forename: Helena
authors.initials: H
authors.lastname: Furberg
authors.forename: Julian
authors.initials: J
authors.lastname: Little
authors.forename: Thomas R
authors.initials: TR
authors.lastname: O'Brien
authors.forename: Daniela
authors.initials: D
authors.lastname: Seminara
authors.forename: Paolo
authors.initials: P
authors.lastname: Vineis
authors.forename: Deborah M
authors.initials: DM
authors.lastname: Winn
authors.forename: Wei
authors.initials: W
authors.lastname: Yu
authors.forename: John P A
authors.initials: JP
authors.lastname: Ioannidis
mesh_terms: D001499:Bayes Theorem; D015982:Bias; D004194:Disease / Q000235:genetics*; D004198:Disease Susceptibility; D004812:Epidemiologic Methods; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D015894:Genome, Human; D055106:Genome-Wide Association Study; D005845:Georgia; D006801:Humans; D033183:Interdisciplinary Communication; D051188:Knowledge Bases; D015201:Meta-Analysis as Topic; D010641:Phenotype; D010865:Pilot Projects; D017410:Practice Guidelines as Topic; D012559:Schizophrenia / Q000235:genetics