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SNP-Based analysis of genetic substructure in the German population

Item Type:Article
Title:SNP-Based analysis of genetic substructure in the German population
Creators Name:Steffens, M. and Lamina, C. and Illig, T. and Bettecken, T. and Vogler, R. and Entz, P. and Suk, E.K. and Toliat, M.R. and Klopp, N. and Caliebe, A. and Koenig, I.R. and Koehler, K. and Luedemann, J. and Lacava, A.D. and Fimmers, R. and Lichtner, P. and Ziegler, A. and Wolf, A. and Krawczak, M. and Nuernberg, P. and Hampe, J. and Schreiber, S. and Meitinger, T. and Wichmann, H.E. and Roeder, K. and Wienker, T.F. and Baur, M.P.
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)). CONCLUSION: 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.
Keywords:German population, Genetic substructure, F-statistics, Genomic control
Source:Human Heredity
Page Range:20-29
Date:October 2006
Official Publication:https://doi.org/10.1159/000095850
PubMed:View item in PubMed

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