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

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


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Case-Control Studies
  • Computer Simulation
  • Control Groups*
  • Data Interpretation, Statistical
  • Databases, Genetic*
  • Diabetes Mellitus, Type 1 / genetics
  • Genetics, Population
  • Genomics / methods*
  • Germany
  • Humans
  • Inheritance Patterns / genetics
  • Polymorphism, Single Nucleotide / genetics*
  • United States