Genome-wide association studies, field synopses, and the development of the knowledge base on genetic variation and human diseases

Muin J. Khoury, Lars Bertram, Paolo Boffetta, Adam S. Butterworth, Stephen J. Chanock, Siobhan M. Dolan, Isabel Fortier, Montserrat Garcia-Closas, Marta Gwinn, Julian P.T. Higgins, A. Cecile J.W. Janssens, James Ostell, Ryan P. Owen, Roberta A. Pagon, Timothy R. Rebbeck, Nathaniel Rothman, Jonine L. Bernstein, Paul R. Burton, Harry Campbell, Anand ChockalingamHelena Furberg, Julian Little, Thomas R. O'Brien, Daniela Seminara, Paolo Vineis, Deborah M. Winn, Wei Yu, John P.A. Ioannidis

Research output: Contribution to journalReview article

115 Scopus citations

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. American Journal of Epidemiology Published by Oxford University Press 2009.2009This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons. org/licenses/by-nc/2.0/uk/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Original languageEnglish (US)
Pages (from-to)269-279
Number of pages11
JournalAmerican Journal of Epidemiology
Volume170
Issue number3
DOIs
StatePublished - Aug 1 2009

Keywords

  • Association
  • Database
  • Encyclopedias
  • Epidemiologic methods
  • Genome, human
  • Genome-wide association study
  • Genomics
  • Meta-analysis

ASJC Scopus subject areas

  • Epidemiology

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    Khoury, M. J., Bertram, L., Boffetta, P., Butterworth, A. S., Chanock, S. J., Dolan, S. M., Fortier, I., Garcia-Closas, M., Gwinn, M., Higgins, J. P. T., Janssens, A. C. J. W., Ostell, J., Owen, R. P., Pagon, R. A., Rebbeck, T. R., Rothman, N., Bernstein, J. L., Burton, P. R., Campbell, H., ... Ioannidis, J. P. A. (2009). Genome-wide association studies, field synopses, and the development of the knowledge base on genetic variation and human diseases. American Journal of Epidemiology, 170(3), 269-279. https://doi.org/10.1093/aje/kwp119