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Genetic Epidemiology (2007) Optimal Designs for Two-Stage Genome-Wide Association Studies
 

Summary: Genetic Epidemiology (2007)
Optimal Designs for Two-Stage Genome-Wide Association Studies
Andrew D. Skol,1,2 Laura J. Scott,1
Gonc-alo R. Abecasis,1
and Michael Boehnke1
1
Department of Biostatistics and Center for Statistical Genetics, University of Michigan, Ann Arbor, Michigan
2
Department of Medicine, Section of Genetic Medicine, University of Chicago, Chicago, Illinois
Genome-wide association (GWA) studies require genotyping hundreds of thousands of markers on thousands of subjects,
and are expensive at current genotyping costs. To conserve resources, many GWA studies are adopting a staged design in
which a proportion of the available samples are genotyped on all markers in stage 1, and a proportion of these markers are
genotyped on the remaining samples in stage 2. We describe a strategy for designing cost-effective two-stage GWA studies.
Our strategy preserves much of the power of the corresponding one-stage design and minimizes the genotyping cost of the
study while allowing for differences in per genotyping cost between stages 1 and 2. We show that the ratio of stage 2 to
stage 1 per genotype cost can strongly influence both the optimal design and the genotyping cost of the study. Increasing the
stage 2 per genotype cost shifts more of the genotyping and study cost to stage 1, and increases the cost of the study. This
higher cost can be partially mitigated by adopting a design with reduced power while preserving the false positive rate or
by increasing the false positive rate while preserving power. For example, reducing the power preserved in the two-stage
design from 99 to 95% that of the one-stage design decreases the two-stage study cost by $15%. Alternatively, the same cost

  

Source: Abecasis, Goncalo - Department of Biostatistics, University of Michigan

 

Collections: Biology and Medicine; Mathematics