gms | German Medical Science

Kongress Medizin und Gesellschaft 2007

17. bis 21.09.2007, Augsburg

How to link call rate, Hardy-Weinberg equilibrium and quality of SNP-data – results from the KORA 500K project

Meeting Abstract

  • Helmut Finner - German Diabetes Center, Leibniz-Institute at the Heinrich-Heine-University, Düsseldorf
  • Klaus Straßburger - German Diabetes Center, Leibniz-Institute at the Heinrich-Heine-University, Düsseldorf
  • Iris M. Heid - GSF-Research Center for Environment and Health, Institute for Epidemiology, Neuherberg
  • Christian Herder - 2German Diabetes Center, Institute of Clinical Diabetology, Leibniz Center at the Heinrich-Heine-University, Düsseldorf
  • Wolfgang Rathmann - German Diabetes Center, Leibniz-Institute at the Heinrich-Heine-University, Düsseldorf
  • Guido Giani - German Diabetes Center, Leibniz-Institute at the Heinrich-Heine-University, Düsseldorf
  • Thorsten Dickhaus - German Diabetes Center, Leibniz-Institute at the Heinrich-Heine-University, Düsseldorf
  • Peter Lichtner - GSF-Research Center for Environment and Health, Institute of Human Genetics, Technical University of Munich, University Hospital Rechts der Isar, Institute of Human Genetics (IHG), Neuherberg, Munich
  • Thomas Meitinger - GSF-Research Center for Environment and Health, Institute of Human Genetics, Technical University of Munich, University Hospital Rechts der Isar, Institute of Human Genetics (IHG), Neuherberg, Munich
  • H.-Erich Wichmann - GSF-Research Center for Environment and Health, Institute for Epidemiology, University of Munich, IBE, Chair of Epidemiology, Neuherberg, Munich
  • Thomas Illig - GSF-Research Center for Environment and Health, Institute for Epidemiology, Neuherberg
  • Christian Gieger - GSF-Research Center for Environment and Health, Institute for Epidemiology, University of Munich, IBE, Chair of Epidemiology, Neuherberg, Munich

Kongress Medizin und Gesellschaft 2007. Augsburg, 17.-21.09.2007. Düsseldorf: German Medical Science GMS Publishing House; 2007. Doc07gmds089

Die elektronische Version dieses Artikels ist vollständig und ist verfügbar unter: http://www.egms.de/de/meetings/gmds2007/07gmds089.shtml

Veröffentlicht: 6. September 2007

© 2007 Finner et al.
Dieser Artikel ist ein Open Access-Artikel und steht unter den Creative Commons Lizenzbedingungen (http://creativecommons.org/licenses/by-nc-nd/3.0/deed.de). Er darf vervielf&aauml;ltigt, verbreitet und &oauml;ffentlich zug&aauml;nglich gemacht werden, vorausgesetzt dass Autor und Quelle genannt werden.


Gliederung

Text

Background: Based on SNP data from the KORA 500K project, a genome-wide association (GWA) study in a population-based German sample of 1644 individuals, we study the impact of the call rate (CR) on Hardy-Weinberg equilibrium (HWE) and the quality of the data.

Materials and methods: KORA (Cooperative Health Research in the Region of Augsburg, Germany) is a population based research platform. In total, four surveys have been conducted. KORA S3 consists of representative samples of 4,856 subjects. In 2003/04, 2,974 participants returned for follow-up (KORA F3). With 1644 of these subjects a genome-wide analysis has been performed using Affymetrix GeneChip 500K arrays containing approximately 500,000 SNPs. Genotypes were determined using the software BRLMM version 1.4.0. We applied statistical tools based on (realized randomized) p-values and the false discovery rate (FDR).

Results: We show that all SNPs with complete genotype information (CR=100%) are nearly perfect in HWE which militates in favor of the population being in HWE. On the other hand, we show that the proportion of SNPs being not in HWE increases linearly with decreasing CR. Hence, it can be argued that failure of HWE is not due to the investigated KORA population but to genotyping errors only.

Conclusion: This finding has important implications for the analysis of GWA studies. The use of a single threshold for HWE p-values as quality criterion cannot be recommended. Instead, a stratified analysis with different thresholds depending on CRs needs to be carried out.