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Human Molecular Genetics Advance Access originally published online on June 27, 2007
Human Molecular Genetics 2007 16(R2):R220-R225; doi:10.1093/hmg/ddm161
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© The Author 2007. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

Successful design and conduct of genome-wide association studies

Christopher I. Amos*

1 Departments of Epidemiology and Bioinformatics and Computational Biology, UT M.D. Anderson Cancer Center, 1155 Pressler Street, Houston, TX 77030, USA

* To whom correspondence should be addressed. Tel: +1 7137923020; Fax: +1 7137928261; Email: camos{at}manderson.org/ camos{at}request.mdacc.tmc.edu

Received June 1, 2007; Revised June 1, 2007; Accepted June 20, 2007

Genome-wide association studies are becoming an increasingly effective tool for identifying genetic factors contributing to complex diseases. In this review, I discuss two sets of genome-wide association studies that identified novel genetic factors for age-related macular degeneration and genetic factors for type II diabetes. In reviewing these sets of studies, my goal is to identify factors that contributed to the success of these studies. Design-related factors include the selection of traits that show strong familiality, the selection of clinically homogeneous populations and the selection of cases that have a family history. Ethnic stratification within the study sample can lead to biases, and methods to control for stratification are briefly reviewed. Finally, the impact of single nucleotide polymorphism selection on the power of a study and procedures for improving power by inferring genotypes, by combining data across studies and by performing multistage analyses are discussed. The continuing success of genome-wide association studies depends on careful selection of populations for study and on collaborative analytical approaches.


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