title: The Population Reference Sample, POPRES: a resource for population, disease, and pharmacological genetics research.
abstract: Technological and scientific advances, stemming in large part from the Human Genome and HapMap projects, have made large-scale, genome-wide investigations feasible and cost effective. These advances have the potential to dramatically impact drug discovery and development by identifying genetic factors that contribute to variation in disease risk as well as drug pharmacokinetics, treatment efficacy, and adverse drug reactions. In spite of the technological advancements, successful application in biomedical research would be limited without access to suitable sample collections. To facilitate exploratory genetics research, we have assembled a DNA resource from a large number of subjects participating in multiple studies throughout the world. This growing resource was initially genotyped with a commercially available genome-wide 500,000 single-nucleotide polymorphism panel. This project includes nearly 6,000 subjects of African-American, East Asian, South Asian, Mexican, and European origin. Seven informative axes of variation identified via principal-component analysis (PCA) of these data confirm the overall integrity of the data and highlight important features of the genetic structure of diverse populations. The potential value of such extensively genotyped collections is illustrated by selection of genetically matched population controls in a genome-wide analysis of abacavir-associated hypersensitivity reaction. We find that matching based on country of origin, identity-by-state distance, and multidimensional PCA do similarly well to control the type I error rate. The genotype and demographic data from this reference sample are freely available through the NCBI database of Genotypes and Phenotypes (dbGaP).
authors.affiliation: GlaxoSmithKline, Research Triangle Park, NC 27709, USA. matthew.r.nelson@gsk.com
authors.forename: Matthew R
authors.initials: MR
authors.lastname: Nelson
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Bryc
authors.forename: Karen S
authors.initials: KS
authors.lastname: King
authors.forename: Amit
authors.initials: A
authors.lastname: Indap
authors.forename: Adam R
authors.initials: AR
authors.lastname: Boyko
authors.forename: John
authors.initials: J
authors.lastname: Novembre
authors.forename: Linda P
authors.initials: LP
authors.lastname: Briley
authors.forename: Yuka
authors.initials: Y
authors.lastname: Maruyama
authors.forename: Dawn M
authors.initials: DM
authors.lastname: Waterworth
authors.forename: Gérard
authors.initials: G
authors.lastname: Waeber
authors.forename: Peter
authors.initials: P
authors.lastname: Vollenweider
authors.forename: Jorge R
authors.initials: JR
authors.lastname: Oksenberg
authors.forename: Stephen L
authors.initials: SL
authors.lastname: Hauser
authors.forename: Heide A
authors.initials: HA
authors.lastname: Stirnadel
authors.forename: Jaspal S
authors.initials: JS
authors.lastname: Kooner
authors.forename: John C
authors.initials: JC
authors.lastname: Chambers
authors.forename: Brendan
authors.initials: B
authors.lastname: Jones
authors.forename: Vincent
authors.initials: V
authors.lastname: Mooser
authors.forename: Carlos D
authors.initials: CD
authors.lastname: Bustamante
authors.forename: Allen D
authors.initials: AD
authors.lastname: Roses
authors.forename: Daniel K
authors.initials: DK
authors.lastname: Burns
authors.forename: Margaret G
authors.initials: MG
authors.lastname: Ehm
authors.forename: Eric H
authors.initials: EH
authors.lastname: Lai