title: On the use of general control samples for genome-wide association studies: genetic matching highlights causal variants.
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.
authors.affiliation: Department of Statistics, Carnegie Mellon University; Pittsburgh, PA 15213, USA.
authors.forename: Diana
authors.initials: D
authors.lastname: Luca
authors.forename: Steven
authors.initials: S
authors.lastname: Ringquist
authors.forename: Lambertus
authors.initials: L
authors.lastname: Klei
authors.forename: Ann B
authors.initials: AB
authors.lastname: Lee
authors.forename: Christian
authors.initials: C
authors.lastname: Gieger
authors.forename: H-Erich
authors.initials: HE
authors.lastname: Wichmann
authors.forename: Stefan
authors.initials: S
authors.lastname: Schreiber
authors.forename: Michael
authors.initials: M
authors.lastname: Krawczak
authors.forename: Ying
authors.initials: Y
authors.lastname: Lu
authors.forename: Alexis
authors.initials: A
authors.lastname: Styche
authors.forename: Bernie
authors.initials: B
authors.lastname: Devlin
authors.forename: Kathryn
authors.initials: K
authors.lastname: Roeder
authors.forename: Massimo
authors.initials: M
authors.lastname: Trucco
mesh_terms: D016022:Case-Control Studies; D003198:Computer Simulation; D035061:Control Groups; D003627:Data Interpretation, Statistical; D030541:Databases, Genetic; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics; D005828:Genetics, Population; D023281:Genomics / Q000379:methods*; D005858:Germany; D006801:Humans; D040582:Inheritance Patterns / Q000235:genetics; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D014481:United States