caa a22 4500 467907293 CHVBK 20180406152838.0 cr unu---uuuuu 170328e20060601xx s 000 0 eng 10.1007/s00251-006-0116-3 doi (NATIONALLICENCE)springer-10.1007/s00251-006-0116-3 Analysing the effect of candidate genes on complex traits: an application in multiple sclerosis [Elektronische Daten] [Tineke Hooper-van Veen, Johannes Berkhof, Chris Polman, Bernard Uitdehaag] The conventional approach of candidate gene studies in complex diseases is to look at the effect of one gene at a time. However, as the outcome of chronic diseases is influenced by a large number of alleles, simultaneous analysis is needed. We demonstrate the application of multivariate regression and cluster analysis to a multiple sclerosis (MS) dataset with genotypes for 489 patients at 11 candidate genes selected on their involvement in the immune response. Using multivariate regression, we observed that different sets of genes were associated with different disease characteristics that reflect different aspects of disease. Out of 15 polymorphisms, we identified one that contributed to the severity of disease. In addition, the set of 15 polymorphisms was predictive for yearly increase in lesion volume as seen on T1-weighted MRI (p=0.044). From this set, no individual polymorphisms could be identified after adjustment for multiple hypotheses testing. By means of a cluster analysis, we aimed to identify subgroups of patients with different pathogenic subtypes of MS on the basis of their genetic profile. We constructed genetic profiles from the genotypes at the 11 candidate genes. The approach proved to be feasible. We observed three clusters in the sample of patients. In this study, we observed no significant differences in the usual clinical and MRI outcome measures between the different clusters. However, a number of consistent trends indicated that this clustering might be related to the course of disease. With a larger number of genes regulating the course of disease, we may be able to identify clinically relevant clusters. The analyses are easily implemented and will be applicable to candidate gene studies of complex traits in general. Springer-Verlag, 2006 Multiple sclerosis nationallicence Genetic nationallicence Prognosis nationallicence Severity nationallicence Hooper-van Veen Tineke Deparment of Molecular Cell Biology and Immunology, VU University Medical Centre, De Boelelaan 1117, 1007 MB, Amsterdam, The Netherlands aut Berkhof Johannes Department of Clinical Epidemiology and Biostatistics, VU University Medical Centre, De Boelelaan 1117, 1007 MB, Amsterdam, The Netherlands aut Polman Chris Department of Neurology, VU University Medical Centre, De Boelelaan 1117, 1007 MB, Amsterdam, The Netherlands aut Uitdehaag Bernard Department of Clinical Epidemiology and Biostatistics, VU University Medical Centre, De Boelelaan 1117, 1007 MB, Amsterdam, The Netherlands aut Immunogenetics Springer-Verlag 58/5-6(2006-06-01), 347-354 0093-7711 58:5-6<347 2006 58 251 https://doi.org/10.1007/s00251-006-0116-3 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s00251-006-0116-3 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Hooper-van Veen Tineke Deparment of Molecular Cell Biology and Immunology, VU University Medical Centre, De Boelelaan 1117, 1007 MB, Amsterdam, The Netherlands aut NATIONALLICENCE 700 1- Berkhof Johannes Department of Clinical Epidemiology and Biostatistics, VU University Medical Centre, De Boelelaan 1117, 1007 MB, Amsterdam, The Netherlands aut NATIONALLICENCE 700 1- Polman Chris Department of Neurology, VU University Medical Centre, De Boelelaan 1117, 1007 MB, Amsterdam, The Netherlands aut NATIONALLICENCE 700 1- Uitdehaag Bernard Department of Clinical Epidemiology and Biostatistics, VU University Medical Centre, De Boelelaan 1117, 1007 MB, Amsterdam, The Netherlands aut NATIONALLICENCE 773 0- Immunogenetics Springer-Verlag 58/5-6(2006-06-01), 347-354 0093-7711 58:5-6<347 2006 58 251 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer