title: SNP-based analysis of genetic substructure in the German population.
abstract: OBJECTIVE
  To evaluate the relevance and necessity to account for the effects of population substructure on association studies under a case-control design in central Europe, we analysed three samples drawn from different geographic areas of Germany. Two of the three samples, POPGEN (n = 720) and SHIP (n = 709), are from north and north-east Germany, respectively, and one sample, KORA (n = 730), is from southern Germany.
  
  
  METHODS
  Population genetic differentiation was measured by classical F-statistics for different marker sets, either consisting of genome-wide selected coding SNPs located in functional genes, or consisting of selectively neutral SNPs from 'genomic deserts'. Quantitative estimates of the degree of stratification were performed comparing the genomic control approach [Devlin B, Roeder K: Biometrics 1999;55:997-1004], structured association [Pritchard JK, Stephens M, Donnelly P: Genetics 2000;155:945-959] and sophisticated methods like random forests [Breiman L: Machine Learning 2001;45:5-32].
  
  
  RESULTS
  F-statistics showed that there exists a low genetic differentiation between the samples along a north-south gradient within Germany (F(ST)(KORA/POPGEN): 1.7 . 10(-4); F(ST)(KORA/SHIP): 5.4 . 10(-4); F(ST)(POPGEN/SHIP): -1.3 . 10(-5)).
  
  
  CONCLUSIONS
  Although the F(ST )-values are very small, indicating a minor degree of population structure, and are too low to be detectable from methods without using prior information of subpopulation membership, such as STRUCTURE [Pritchard JK, Stephens M, Donnelly P: Genetics 2000;155:945-959], they may be a possible source for confounding due to population stratification.
authors.affiliation: Institute of Medical Biometry, Informatics and Epidemiology, Rheinische Friedrich-Wilhelms-University, Bonn, Germany. steffens@imbie.meb.uni-bonn.de
authors.forename: Michael
authors.initials: M
authors.lastname: Steffens
authors.forename: Claudia
authors.initials: C
authors.lastname: Lamina
authors.forename: Thomas
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authors.lastname: Illig
authors.forename: Thomas
authors.initials: T
authors.lastname: Bettecken
authors.forename: Rainer
authors.initials: R
authors.lastname: Vogler
authors.forename: Patricia
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authors.lastname: Entz
authors.forename: Eun-Kyung
authors.initials: EK
authors.lastname: Suk
authors.forename: Mohammad Reza
authors.initials: MR
authors.lastname: Toliat
authors.forename: Norman
authors.initials: N
authors.lastname: Klopp
authors.forename: Amke
authors.initials: A
authors.lastname: Caliebe
authors.forename: Inke R
authors.initials: IR
authors.lastname: König
authors.forename: Karola
authors.initials: K
authors.lastname: Köhler
authors.forename: Jan
authors.initials: J
authors.lastname: Ludemann
authors.forename: Amalia
authors.initials: A
authors.lastname: Diaz Lacava
authors.forename: Rolf
authors.initials: R
authors.lastname: Fimmers
authors.forename: Peter
authors.initials: P
authors.lastname: Lichtner
authors.forename: Andreas
authors.initials: A
authors.lastname: Ziegler
authors.forename: Andreas
authors.initials: A
authors.lastname: Wolf
authors.forename: Michael
authors.initials: M
authors.lastname: Krawczak
authors.forename: Peter
authors.initials: P
authors.lastname: Nūrnberg
authors.forename: Jochen
authors.initials: J
authors.lastname: Hampe
authors.forename: Stefan
authors.initials: S
authors.lastname: Schreiber
authors.forename: Thomas
authors.initials: T
authors.lastname: Meitinger
authors.forename: H-Erich
authors.initials: HE
authors.lastname: Wichmann
authors.forename: Kathryn
authors.initials: K
authors.lastname: Roeder
authors.forename: Thomas F
authors.initials: TF
authors.lastname: Wienker
authors.forename: Max P
authors.initials: MP
authors.lastname: Baur
mesh_terms: D016022:Case-Control Studies; D014644:Genetic Variation; D005828:Genetics, Population / Q000379:methods*; D015894:Genome, Human; D005838:Genotype; D005858:Germany; D006801:Humans; D008957:Models, Genetic; D020641:Polymorphism, Single Nucleotide; D044382:Population Groups