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Am J Hum Genet. 2008 Feb;82(2):453-63. doi: 10.1016/j.ajhg.2007.11.003. Epub 2008 Jan 24.

On the use of general control samples for genome-wide association studies: genetic matching highlights causal variants.

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1
Department of Statistics, Carnegie Mellon University; Pittsburgh, PA 15213, USA.

Abstract

Resources being amassed for genome-wide association (GWA) studies include "control databases" genotyped with a large-scale SNP array. How to use these databases effectively is an open question. We develop a method to match, by genetic ancestry, controls to affected individuals (cases). The impact of this method, especially for heterogeneous human populations, is to reduce the false-positive rate, inflate other spuriously small p values, and have little impact on the p values associated with true positive loci. Thus, it highlights true positives by downplaying false positives. We perform a GWA by matching Americans with type 1 diabetes (T1D) to controls from Germany. Despite the complex study design, these analyses identify numerous loci known to confer risk for T1D.

PMID:
18252225
PMCID:
PMC2427172
DOI:
10.1016/j.ajhg.2007.11.003
[Indexed for MEDLINE]
Free PMC Article
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