title: Improved prediction of complex diseases by common genetic markers: state of the art and further perspectives.
abstract: Reliable risk assessment of frequent, but treatable diseases and disorders has considerable clinical and socio-economic relevance. However, as these conditions usually originate from a complex interplay between genetic and environmental factors, precise prediction remains a considerable challenge. The current progress in genotyping technology has resulted in a substantial increase of knowledge regarding the genetic basis of such diseases and disorders. Consequently, common genetic risk variants are increasingly being included in epidemiological models to improve risk prediction. This work reviews recent high-quality publications targeting the prediction of common complex diseases. To be included in this review, articles had to report both, numerical measures of prediction performance based on traditional (non-genetic) risk factors, as well as measures of prediction performance when adding common genetic variants to the model. Systematic PubMed-based search finally identified 55 eligible studies. These studies were compared with respect to the chosen approach and methodology as well as results and clinical impact. Phenotypes analysed included tumours, diabetes mellitus, and cardiovascular diseases. All studies applied one or more statistical measures reporting on calibration, discrimination, or reclassification to quantify the benefit of including SNPs, but differed substantially regarding the methodological details that were reported. Several examples for improved risk assessments by considering disease-related SNPs were identified. Although the add-on benefit of including SNP genotyping data was mostly moderate, the strategy can be of clinical relevance and may, when being paralleled by an even deeper understanding of disease-related genetics, further explain the development of enhanced predictive and diagnostic strategies for complex diseases.
authors.affiliation: Department of Cell Therapy, Fraunhofer Institute for Cell Therapy and Immunology, Perlickstraße 1, Leipzig, Germany. bent.mueller@izi.fraunhofer.de.
authors.forename: Bent
authors.initials: B
authors.lastname: Müller
authors.affiliation: Department of Cell Therapy, Fraunhofer Institute for Cell Therapy and Immunology, Perlickstraße 1, Leipzig, Germany.|Translational Center for Regenerative Medicine, Leipzig, Germany.
authors.forename: Arndt
authors.initials: A
authors.lastname: Wilcke
authors.affiliation: Department of Medical Informatics, Biometry and Epidemiology, University of Munich, Munich, Germany.
authors.forename: Anne-Laure
authors.initials: AL
authors.lastname: Boulesteix
authors.affiliation: Department of Neuropsychology, Max Planck Institute for Human Cognitive and Brain Sciences, Leipzig, Germany.
authors.forename: Jens
authors.initials: J
authors.lastname: Brauer
authors.affiliation: Institute for Human Genetics, University Hospital Leipzig, University of Leipzig, Leipzig, Germany.|Institute for Human Genetics, University Hospital Essen, University of Duisburg-Essen, Essen, Germany.
authors.forename: Eberhard
authors.initials: E
authors.lastname: Passarge
authors.affiliation: Department of Cell Therapy, Fraunhofer Institute for Cell Therapy and Immunology, Perlickstraße 1, Leipzig, Germany.|Translational Center for Regenerative Medicine, Leipzig, Germany.|Massachusetts General Hospital and Harvard Medical School, Stroke and Neurovascular Regulation Laboratory, Charlestown, MA, USA.|Fraunhofer Research Institution of Marine Biotechnology and Institute for Medical and Marine Biotechnology, University of Lübeck, Lübeck, Germany.
authors.forename: Johannes
authors.initials: J
authors.lastname: Boltze
authors.affiliation: Department of Cell Therapy, Fraunhofer Institute for Cell Therapy and Immunology, Perlickstraße 1, Leipzig, Germany.|Translational Center for Regenerative Medicine, Leipzig, Germany.|Institute for Medical Informatics, Statistics and Epidemiology and LIFE-Leipzig Research Center for Civilization Diseases, University of Leipzig, Leipzig, Germany.
authors.forename: Holger
authors.initials: H
authors.lastname: Kirsten
mesh_terms: D002318:Cardiovascular Diseases / Q000175:diagnosis / Q000235:genetics*; D003920:Diabetes Mellitus / Q000175:diagnosis / Q000235:genetics*; D005819:Genetic Markers; D060005:Genotyping Techniques; D006801:Humans; D009369:Neoplasms / Q000175:diagnosis / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D018570:Risk Assessment
chemical_list: D005819:Genetic Markers
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