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.
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.
Authors: Christina Holzapfel; Harald Grallert; Jens Baumert; Barbara Thorand; Angela Döring; H Erich Wichmann; Hans Hauner; Thomas Illig; Andreas Mielck Journal: J Epidemiol Community Health Date: 2010-07-13 Impact factor: 3.710
Authors: C Holzapfel; H Grallert; C Huth; S Wahl; B Fischer; A Döring; I M Rückert; A Hinney; J Hebebrand; H-E Wichmann; H Hauner; T Illig; I M Heid Journal: Int J Obes (Lond) Date: 2010-04-13 Impact factor: 5.095
Authors: Gabriel Cuellar-Partida; Yi Lu; Pik Fang Kho; Alex W Hewitt; H-Erich Wichmann; Seyhan Yazar; Dwight Stambolian; Joan E Bailey-Wilson; Robert Wojciechowski; Jie Jin Wang; Paul Mitchell; David A Mackey; Stuart MacGregor Journal: Genet Epidemiol Date: 2015-10-26 Impact factor: 2.135
Authors: Carla I G Vogel; André Scherag; Günter Brönner; Thuy T Nguyen; Hai-Jun Wang; Harald Grallert; Alexa Bornhorst; Dieter Rosskopf; Henry Völzke; Thomas Reinehr; Winfried Rief; Thomas Illig; H-Erich Wichmann; Helmut Schäfer; Johannes Hebebrand; Anke Hinney Journal: BMC Med Genet Date: 2009-03-02 Impact factor: 2.103
Authors: Chantel D Sloan; Angeline D Andrew; Eric J Duell; Scott M Williams; Margaret R Karagas; Jason H Moore Journal: PLoS One Date: 2009-09-07 Impact factor: 3.240