Quantification of impact of genetic variants (2004-2013)
Study objectives:
The aim of this methodological project is to investigate, improve and apply approaches to judge the impact of genetic variants in genetic epidemiological research, which has a special current focus on survival models for cohort data.
Specific aims:
Adaptation of methods for genetic association analysis (e.g. modelling techniques, haplotype estimation) for special study designs in genetic epidemiological research, which include:
- Time-to-onset analysis (survival phenotypes)
- Cohort data analysis (longitudinal phenotypes)
- Analysis within case-cohort data
- Applicability for genome-wide association analysis
Study population:
Cross-sectional KORA surveys, cohort data with survival information, KORA case-cohort.
Study team location:
Helmholtz Zentrum München, German Research Center for Environmental Health.
Study methods:
Application and comparison of existing and new criteria proposed for application as judgement tools through real data analysis as well as simulations studies.
Study period:
2004-2013
Current status:
Modelling of SNPs and haplotypes has been adapted to cohort as well as case-cohort data. Several manuscripts incorporating these techniques have been published. A general recommendation of a criterion judging the impact of genetic variants within time-to-onset analysis has been found (manuscript in press). Applicability to case-cohort design and genome-wide association studies is a current investigation.
Investigators:
Martina Müller, Iris M. Heid (coordinator), H.-Erich Wichmann: Helmholtz Zentrum München
Internal participants:
Jens Baumert, Barbara Thorand, Melanie Kolz, Thomas Illig, Norman Klopp.
Collaborators:
H. Bickeböller, GAU, University of Göttingen, Department of Genetic Epidemiology; W. König, Department of Internal Medicine II–Cardiology, University of Ulm Medical Centre, Ulm; C. Herder, Institute for Clinical Diabetes Research, German Diabetes Centre, Leibniz Centre at Heinrich Heine University, Düsseldorf; F. Kronenberg, Division of Genetic Epidemiology, Department of Medical Genetics, Molecular and Clinical Pharmacology, Innsbruck Medical University, Innsbruck, Austria.
Funding:
BMBF-NGFN-2, NGFNplus Atherogenomics, LMU (Center of Excellence)
Contact:
martina.mueller@helmholtz-muenchen.de
wichmann@helmholtz-muenchen.de
Selected publications:
Müller, M., Döring, A., Küchenhoff, H., Lamina, C., Malzahn, D., Bickeböller, H., Vollmert, C., Klopp, N., Meisinger, C., Heinrich, J., Kronenberg, F., Wichmann, H.-E., Heid, I.M.: Quantifying the contribution of genetic variants for survival phenotypes. Genetic Epidemiology. In press
Kolz, M., Baumert, J., Müller, M., Khuseyinova, N., Klopp, N., Thorand, B., Meisinger, C., Herder, C., Koenig, W. and Illig, T.:
Association between variations in the TLR4 gene and incident type 2 diabetes is modified by the ratio of total cholesterol to HDL-cholesterol.
BMC Medical Genetics. Stand 01/2008 (accepted)
Herder, C., Illig, T., Baumert, J., Müller, M., Klopp, N., Khuseyinova, N., Meisinger, C., Martin, S., Thorand, B., Koenig, W.:
Macrophage migration inhibitory factor (MIF) and risk for coronary heart disease: Results from the MONICA/KORA Augsburg Case-Cohort Study, 1984-2002.
Atherosclerosis. Stand 12/2007 (accepted)
Herder, C., Klopp, N., Baumert, J., Müller, M., Khuseyinova, N., Meisinger, C., Martin, S., Illig, T., Koenig, W., Thorand, B.:
Effect of macrophage migration inhibitory factor (MIF) gene variants and MIF serum concentrations on the risk of type 2 diabetes: results from the MONICA/KORA Augsburg Case Cohort Study, 1984-2002.
Diabetologia, 2008 Feb;51(2):276-84. Epub 2007 Aug 22
Kolz, M., Koenig, W., Müller, M., Andreani, M., Greven, S., Illig, T., Khuseyinova, N., Panagiotakos, D., Pershagen, G., Salomaa, V., Sunyer, J., Peters, A., for the AIRGENE Study Group:
DNA variants, plasma levels and variability of C-reactive protein in Myocardial infarction survivors: results from the AIRGENE study.
Eur Heart J, Stand 11/2007: epub ahead of print
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