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Concordance for disease course and age of onset in Scandinavian multiple sclerosis coaffected sib pairs

Department of Neurology, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark, annette{at}oturai.net

Lars P Ryder

Department of Clinical Immunology, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark

Sten Fredrikson

Department of Neurology, Huddinge University Hospital, Karolinska Institute, Huddinge, Sweden

Kjell-Morten Myhr

The Multiple Sclerosis National Competence Center, Department of Neurology, Haukeland University Hospital, Bergen, Norway

Elisabeth G Celius

Department of Neurology, UllevaSl University Hospital, Oslo, Norway

Hanne Flinstad Harbo

Institute of Immunology, The National Hospital, Oslo, Norway

Oluf Andersen

Department of Neurology, Göteborg University Hospital, Göteborg, Sweden

Eva ASkesson

Department of Neurology, Huddinge University Hospital, Karolinska Institute, Huddinge, Sweden

Jan Hillert

Department of Neurology, Huddinge University Hospital, Karolinska Institute, Huddinge, Sweden

Hans O Madsen

Department of Clinical Immunology, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark

Harald Nyland

The Multiple Sclerosis National Competence Center, Department of Neurology, Haukeland University Hospital, Bergen, Norway

Anne Spurkland

Institute of Immunology, The National Hospital, Oslo, Norway

Pameli Datta

Department of Neurology, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark

Arne Svejgaard

Department of Clinical Immunology, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark

Per S Sorensen

Department of Neurology, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark

Background: Investigation of coaffected sib pairs is one method to determine the genetic influence on the clinical presentatio n of many complex diseases, such as multiple sclerosis (MS). Investigation of the clinical concordance in coaffected sib pairs may be a prerequisite to identify genes that modify the clinical outcome. The aim of this study was to investigate a possible genetic influence on selected demographic and clinical variables among familial Scandinavian MS cases. Material and methods: We identified 136 C aucasian Scandinavian families with MS coaffected sib pairs from Denmark, Norway, and Sweden. C ohen’s kappa coefficient and the intraclass correlation coefficient were used to assess concordances in sib pairs. Furthermore, clinical features and HLA-DR2 carrier status were compared among the probands of sib pairs. Results: We found significant concordance of the disease course (k=0.28, PB-0.001) and adjusted age of onset (r =0.23, P=0.028). Among probands of sib pairs, HLA-DR2 carrier patients had a younger age of onset (P=0.024). Conclusion: A nalyses of Scandinavian coaffected sib pairs suggest that disease course and age of onset are partly under genetic control. Furthermore, HLA-DR2 in probands of sib pairs suggests importance for age of onset.

Key Words: clinical features • HLA • multiple sclerosis • sib pairs

Multiple Sclerosis, Vol. 10, No. 1, 5-8 (2004)
DOI: 10.1191/1352458504ms975oa


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