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Am J Hum Genet. 2007 Aug;81(2):397-404. Epub 2007 Jun 26.

Enriching the analysis of genomewide association studies with hierarchical modeling.

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  • 1Department of Epidemiology and Biostatistics, University of California-San Francisco, San Francisco, CA 94143-0794, USA.


Genomewide association studies (GWAs) initially investigate hundreds of thousands of single-nucleotide polymorphisms (SNPs), and the most promising SNPs are further evaluated with additional subjects, for replication or a joint analysis. Deciding which SNPs merit follow-up is one of the most crucial aspects of these studies. We present here an approach for selecting the most-promising SNPs that incorporates into a hierarchical model both conventional results and other existing information about the SNPs. The model is developed for general use, its potential value is shown by application, and tools are provided for undertaking hierarchical modeling. By quantitatively harnessing all available information in GWAs, hierarchical modeling may more clearly distinguish true causal variants from noise.

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