title: An evaluation of the genetic-matched pair study design using genome-wide SNP data from the European population.
abstract: Genetic matching potentially provides a means to alleviate the effects of incomplete Mendelian randomization in population-based gene-disease association studies. We therefore evaluated the genetic-matched pair study design on the basis of genome-wide SNP data (309,790 markers; Affymetrix GeneChip Human Mapping 500K Array) from 2457 individuals, sampled at 23 different recruitment sites across Europe. Using pair-wise identity-by-state (IBS) as a matching criterion, we tried to derive a subset of markers that would allow identification of the best overall matching (BOM) partner for a given individual, based on the IBS status for the subset alone. However, our results suggest that, by following this approach, the prediction accuracy is only notably improved by the first 20 markers selected, and increases proportionally to the marker number thereafter. Furthermore, in a considerable proportion of cases (76.0%), the BOM of a given individual, based on the complete marker set, came from a different recruitment site than the individual itself. A second marker set, specifically selected for ancestry sensitivity using singular value decomposition, performed even more poorly and was no more capable of predicting the BOM than randomly chosen subsets. This leads us to conclude that, at least in Europe, the utility of the genetic-matched pair study design depends critically on the availability of comprehensive genotype information for both cases and controls.
authors.affiliation: Institut für Medizinische Informatik und Statistik, Christian-Albrechts-Universität Kiel, Kiel, Germany.
authors.forename: Timothy Tehua
authors.initials: TT
authors.lastname: Lu
authors.forename: Oscar
authors.initials: O
authors.lastname: Lao
authors.forename: Michael
authors.initials: M
authors.lastname: Nothnagel
authors.forename: Olaf
authors.initials: O
authors.lastname: Junge
authors.forename: Sandra
authors.initials: S
authors.lastname: Freitag-Wolf
authors.forename: Amke
authors.initials: A
authors.lastname: Caliebe
authors.forename: Miroslava
authors.initials: M
authors.lastname: Balascakova
authors.forename: Jaume
authors.initials: J
authors.lastname: Bertranpetit
authors.forename: Laurence Albert
authors.initials: LA
authors.lastname: Bindoff
authors.forename: David
authors.initials: D
authors.lastname: Comas
authors.forename: Gunilla
authors.initials: G
authors.lastname: Holmlund
authors.forename: Anastasia
authors.initials: A
authors.lastname: Kouvatsi
authors.forename: Milan
authors.initials: M
authors.lastname: Macek
authors.forename: Isabelle
authors.initials: I
authors.lastname: Mollet
authors.forename: Finn
authors.initials: F
authors.lastname: Nielsen
authors.forename: Walther
authors.initials: W
authors.lastname: Parson
authors.forename: Jukka
authors.initials: J
authors.lastname: Palo
authors.forename: Rafal
authors.initials: R
authors.lastname: Ploski
authors.forename: Antti
authors.initials: A
authors.lastname: Sajantila
authors.forename: Adriano
authors.initials: A
authors.lastname: Tagliabracci
authors.forename: Ulrik
authors.initials: U
authors.lastname: Gether
authors.forename: Thomas
authors.initials: T
authors.lastname: Werge
authors.forename: Fernando
authors.initials: F
authors.lastname: Rivadeneira
authors.forename: Albert
authors.initials: A
authors.lastname: Hofman
authors.forename: André Gerardus
authors.initials: AG
authors.lastname: Uitterlinden
authors.forename: Christian
authors.initials: C
authors.lastname: Gieger
authors.forename: Heinz-Erich
authors.initials: HE
authors.lastname: Wichmann
authors.forename: Andreas
authors.initials: A
authors.lastname: Ruether
authors.forename: Stefan
authors.initials: S
authors.lastname: Schreiber
authors.forename: Christian
authors.initials: C
authors.lastname: Becker
authors.forename: Peter
authors.initials: P
authors.lastname: Nürnberg
authors.forename: Matthew Roberts
authors.initials: MR
authors.lastname: Nelson
authors.forename: Manfred
authors.initials: M
authors.lastname: Kayser
authors.forename: Michael
authors.initials: M
authors.lastname: Krawczak
mesh_terms: D004247:DNA / Q000032:analysis / Q000235:genetics; D005060:Europe; D005260:Female; D005819:Genetic Markers; D014644:Genetic Variation; D015894:Genome, Human; D055106:Genome-Wide Association Study; D006801:Humans; D008297:Male; D016555:Matched-Pair Analysis; D020641:Polymorphism, Single Nucleotide; D044382:Population Groups / Q000235:genetics; D012107:Research Design; D017422:Sequence Analysis, DNA
chemical_list: D005819:Genetic Markers; D004247:DNA