Population-genetic comparison of the Sorbian isolate population in Germany with the German KORA population using genome-wide SNP arrays

BMC Genetics

Research Article

Michael Stumvoll¹  Anke Tönjes¹  John Novembre²  Krishna R Veeramah³  Ina-Maria Rueckert⁴  Christian Gieger⁴  Heinz-Erich Wichmann⁵  Arnd Gross⁶  Markus Loeffler⁶  Markus Scholz⁶  Peter Ahnert⁶  Nab R Roshyara⁶  Peter Kovacs⁷  Mark Stoneking⁸ 

[1] Department of Medicine, University of Leipzig, Liebigstrasse 18, 04103, Leipzig, Germany;IFB Adiposity Diseases, University of Leipzig, Stephanstrasse 9c, 04103, Leipzig, Germany;Dept Eco & Evo Biol, Interdepartmental Program in Bioinformatics, University of California, Box 951606, 621 Charles E. Young Dr South, 90095-1606, Los Angeles, Los Angeles, CA, USA;Dept Eco & Evo Biol, Interdepartmental Program in Bioinformatics, University of California, Box 951606, 621 Charles E. Young Dr South, 90095-1606, Los Angeles, Los Angeles, CA, USA;Center for Society and Genetics, University of California, Box 957221, 1323 Rolfe Hall, 90095-7221, Los Angeles, Los Angeles, CA, USA;Dept of History, University of California, Box 951473, 6265 Bunche Hall, 90095-1473, Los Angeles, Los Angeles, CA, USA;Helmholtz Centre Munich, German Research Center for Environmental Health, Institute of Epidemiology, Ingolstaedter Landstraße 1, 85764, Neuherberg, Germany;Helmholtz Centre Munich, German Research Center for Environmental Health, Institute of Epidemiology, Ingolstaedter Landstraße 1, 85764, Neuherberg, Germany;Institute of Medical Informatics, Biometry and Epidemiology, Chair of Epidemiology, Ludwig-Maximilians-University, Marchioninistraße 15, 81377, Munich, Germany;Klinikum Grosshadern, Ludwig Maximilians University, Marchioninistraße 15, 81377, Munich, Germany;Institute for Medical Informatics, Statistics and Epidemiology, University of Leipzig, Haertelstrasse 16-18, 04107, Leipzig, Germany;LIFE Center (Leipzig Interdisciplinary Research Cluster of Genetic Factors, Phenotypes and Environment), University of Leipzig, Philipp-Rosenthal Strasse 27, 04103, Leipzig, Germany;Interdisciplinary Center for Clinical Research, University of Leipzig, Liebigstrasse 21, 04103, Leipzig, Germany;Max Planck Institute for Evolutionary Anthropology, Deutscher Platz 6, 04103, Leipzig, Germany;

关键词: Linkage Disequilibrium;    Sorb;    Genetic Association Study;    Linkage Disequilibrium Structure;    Kora Sample;   

DOI  :  10.1186/1471-2156-12-67

 received in 2011-03-14, accepted in 2011-07-28,  发布年份 2011

来源: Springer

【 摘 要 】

BackgroundThe Sorbs are an ethnic minority in Germany with putative genetic isolation, making the population interesting for disease mapping. A sample of N = 977 Sorbs is currently analysed in several genome-wide meta-analyses. Since genetic differences between populations are a major confounding factor in genetic meta-analyses, we compare the Sorbs with the German outbred population of the KORA F3 study (N = 1644) and other publically available European HapMap populations by population genetic means. We also aim to separate effects of over-sampling of families in the Sorbs sample from effects of genetic isolation and compare the power of genetic association studies between the samples.ResultsThe degree of relatedness was significantly higher in the Sorbs. Principal components analysis revealed a west to east clustering of KORA individuals born in Germany, KORA individuals born in Poland or Czech Republic, Half-Sorbs (less than four Sorbian grandparents) and Full-Sorbs. The Sorbs cluster is nearest to the cluster of KORA individuals born in Poland. The number of rare SNPs is significantly higher in the Sorbs sample. FST between KORA and Sorbs is an order of magnitude higher than between different regions in Germany. Compared to the other populations, Sorbs show a higher proportion of individuals with runs of homozygosity between 2.5 Mb and 5 Mb. Linkage disequilibrium (LD) at longer range is also slightly increased but this has no effect on the power of association studies.Oversampling of families in the Sorbs sample causes detectable bias regarding higher FST values and higher LD but the effect is an order of magnitude smaller than the observed differences between KORA and Sorbs. Relatedness in the Sorbs also influenced the power of uncorrected association analyses.ConclusionsSorbs show signs of genetic isolation which cannot be explained by over-sampling of relatives, but the effects are moderate in size. The Slavonic origin of the Sorbs is still genetically detectable.Regarding LD structure, a clear advantage for genome-wide association studies cannot be deduced. The significant amount of cryptic relatedness in the Sorbs sample results in inflated variances of Beta-estimators which should be considered in genetic association analyses.

【 授权许可】

Unknown   
© Gross et al; licensee BioMed Central Ltd. 2011. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.