On the Use of General Control Samples for Genome-wide Association Studies: Genetic Matching Highlights Causal Variants

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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. © 2008 The American Society of Human Genetics.

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Luca, D., Ringquist, S., Klei, L., Lee, A. B., Gieger, C., Wichmann, H. E., … Trucco, M. (2008). On the Use of General Control Samples for Genome-wide Association Studies: Genetic Matching Highlights Causal Variants. American Journal of Human Genetics, 82(2), 453–463. https://doi.org/10.1016/j.ajhg.2007.11.003

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