Skip Navigation



IJE Advance Access published online on December 20, 2006
International Journal of Epidemiology, doi:10.1093/ije/dyl253
This Article
Right arrow Full Text Freely available
Right arrow FREE Full Text (PDF) Freely available
Right arrowOA All Versions of this Article:
36/2/439    most recent
dyl253v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Google Scholar
Right arrow Articles by Khoury, M. J
Right arrow Articles by Ioannidis, J. P.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Khoury, M. J
Right arrow Articles by Ioannidis, J. P.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

Published by Oxford University Press on behalf of the International Epidemiological Association.
The online version of this article has been published under an open access model. Users are entitled to use, reproduce, disseminate, or display the open access version of this article for non-commercial purposes provided that: the original authorship is properly and fully attributed; the Journal and Oxford University Press are attributed as the original place of publication with the correct citation details given; if an article is subsequently reproduced or disseminated not in its entirety but only in part or as a derivative work this must be clearly indicated. For commercial re-use, please contact journals.permissions@oxfordjournals.org

On the synthesis and interpretation of consistent but weak gene–disease associations in the era of genome-wide association studies

Muin J Khoury1,*, Julian Little2, Marta Gwinn1 and John PA Ioannidis3

1National Office of Public Health Genomics, Coordinating Center for Health Promotion, Centers for Disease Control and Prevention.
2Canada Research Chair in Human Genome Epidemiology, Department of Epidemiology and Community Medicine, University of Ottawa, Ottawa, Canada.
3Department of Hygiene and Epidemiology University of Ioannina School of Medicine, Ioannina, Greece and Department of Medicine, Tufts University School of Medicine, Boston, USA.

* Corresponding author. National Office of Public Health Genomics, Centers for Disease Control and Prevention, 4770 Buford Hwy, Atlanta GA 30341 USA (mailstop K89). E-mail: mkhoury{at}cdc.gov


  Abstract

Emerging technologies are allowing researchers to study hundreds of thousands of genetic variants simultaneously as risk factors for common complex diseases. Both theoretical considerations and empirical evidence suggest that specific genetic variants causally associated with common diseases will have small effects (risk ratios mostly <2.0). However, the combination of even a few small effects (e.g. effects of fewer than 20 common genetic variants) could account for a sizeable population attributable fraction of common diseases and shed important light on disease pathogenesis and environmental determinants. Nevertheless, the inauguration of genome-wide association studies only magnifies the challenge of differentiating between the expected, true weak associations from the numerous spurious effects caused by misclassification, confounding and significance-chasing biases. Standards are urgently needed for presenting and interpreting cumulative evidence on gene–disease associations, especially for consistent but weak associations. Criteria for synthesis of the evidence should include sound methods for study conduct and analysis, biological plausibility, experimental evidence and adequate replication in large-scale, collaborative studies. Efforts by the Human Genome Epidemiology Network (HuGENet) are currently ongoing to streamline and operationalize these criteria for data on genetic associations with common diseases.

Keywords Epidemiological methods, genomics, risk ratios, genome-wide analysis

Accepted 21 October 2006


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?


This article has been cited by other articles:


Home page
 Int J EpidemiolHome page
P. R Burton, A. L Hansell, I. Fortier, T. A Manolio, M. J Khoury, J. Little, and P. Elliott
Size matters: just how big is BIG?: Quantifying realistic sample size requirements for human genome epidemiology
Int. J. Epidemiol., August 25, 2008; (2008) dyn147v2.
[Abstract] [Full Text] [PDF]

Home page
 Schizophr BullHome page
J. Welham, M. Isohanni, P. Jones, and J. McGrath
The Antecedents of Schizophrenia: A Review of Birth Cohort Studies
Schizophr Bull, July 24, 2008; (2008) sbn084v1.
[Abstract] [Full Text] [PDF]

Home page
 Int J EpidemiolHome page
G. D. Smith
'Something funny seems to happen': J.B.S. Haldane and our chaotic, complex but understandable world
Int. J. Epidemiol., June 1, 2008; 37(3): 423 - 426.
[Full Text] [PDF]

Home page
 J Mol EndocrinolHome page
M. Plourde, C. Manhes, G. Leblanc, F. Durocher, M. Dumont, O. Sinilnikova, I. BRCAs, and J. Simard
Mutation analysis and characterization of HSD17B2 sequence variants in breast cancer cases from French Canadian families with high risk of breast and ovarian cancer
J. Mol. Endocrinol., April 1, 2008; 40(4): 161 - 172.
[Abstract] [Full Text] [PDF]

Home page
 JAMAHome page
T. A. Pearson and T. A. Manolio
How to Interpret a Genome-wide Association Study
JAMA, March 19, 2008; 299(11): 1335 - 1344.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Epidemiol. Biomarkers Prev.Home page
M. Gwinn, I. Guessous, and M. Khoury
"Intention to Analyze" in Pharmacogenomics Studies
Cancer Epidemiol. Biomarkers Prev., March 1, 2008; 17(3): 740 - 740.
[Full Text] [PDF]

Home page
 JAMAHome page
A. M. Bennet, E. Di Angelantonio, Z. Ye, F. Wensley, A. Dahlin, A. Ahlbom, B. Keavney, R. Collins, B. Wiman, U. de Faire, et al.
Association of Apolipoprotein E Genotypes With Lipid Levels and Coronary Risk
JAMA, September 19, 2007; 298(11): 1300 - 1311.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Epidemiol. Biomarkers Prev.Home page
C. M. McBride and L. C. Brody
Point: Genetic Risk Feedback for Common Disease Time to Test the Waters
Cancer Epidemiol. Biomarkers Prev., September 1, 2007; 16(9): 1724 - 1726.
[Full Text] [PDF]

Home page
 Int J EpidemiolHome page
H Campbell and T Manolio
Commentary: Rare alleles, modest genetic effects and the need for collaboration
Int. J. Epidemiol., April 1, 2007; 36(2): 445 - 448.
[Full Text] [PDF]


Disclaimer:
Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.