Genome-wide association studies, field synopses, and the development of the knowledge base on genetic variation and human diseases.
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.
Khoury
Muin J
MJ
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
Bertram
Lars
L
Boffetta
Paolo
P
Butterworth
Adam S
AS
Chanock
Stephen J
SJ
Dolan
Siobhan M
SM
Fortier
Isabel
I
Garcia-Closas
Montserrat
M
Gwinn
Marta
M
Higgins
Julian P T
JP
Janssens
A Cecile J W
AC
Ostell
James
J
Owen
Ryan P
RP
Pagon
Roberta A
RA
Rebbeck
Timothy R
TR
Rothman
Nathaniel
N
Bernstein
Jonine L
JL
Burton
Paul R
PR
Campbell
Harry
H
Chockalingam
Anand
A
Furberg
Helena
H
Little
Julian
J
O'Brien
Thomas R
TR
Seminara
Daniela
D
Vineis
Paolo
P
Winn
Deborah M
DM
Yu
Wei
W
Ioannidis
John P A
JP
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