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Familial clustering of multiple sclerosis in a Dutch genetic isolate

Department of Neurology, MS Centre ErasMS, Erasmus MC, Rotterdam, 3015 GD, the Netherlands

LM Pardo Cortes

Y S Aulchenko

Departments of Epidemiology and Biostatistics, Genetic Epidemiology Unit, Erasmus MC, Rotterdam, 3015 GD, the Netherlands

K Sintnicolaas

Sanquin Blood Bank South West Region, Rotterdam, 3015 CN, the Netherlands

O Njajou

P JLM Snijders

Departments of Epidemiology and Biostatistics, Genetic Epidemiology Unit, Erasmus MC, Rotterdam, 3015 GD, the Netherlands

B A Oostra

Clinical Genetics, Erasmus MC, Rotterdam, 3015 GD, the Netherlands

C M van Duijn

Departments of Epidemiology and Biostatistics, Genetic Epidemiology Unit, Erasmus MC, Rotterdam, 3015 GD, the Netherlands

R Q Hintzen

Department of Neurology, MS Centre ErasMS, Erasmus MC, Rotterdam, 3015 GD, the Netherlands

Multiple sclerosis (MS) is a complex disease with a substantial, yet poorly identified, genetic influence. We estimated the pattern of familial aggregation of MS in a recent genetically isolated population in the Netherlands. Forty-eight MS patients were identified. Their relationship was evaluated by tracing extended pedigrees, making use of municipal and church records. Of the 48 MS patients, 24 could be linked to a common ancestor in 14 generations. However, multiple relationships exist between patients and, to take these into account, we calculated inbreeding and kinship coefficients. We found that MS patients from the isolate were significantly more often related to each other and significantly more often inbred than a non-MS control group, drawn from the same isolate. There was no clustering of Type 1 diabetes and autoimmune thyroid diseases in families of MS patients from this isolate. Finally, HLA typing was performed. Although there was a trend towards a higher prevalence of the HLA DRB1*15 allele in patients compared to controls, differences did not reach significance. This study suggests familial aggregation in the genetically isolated population. The high level of inbreeding makes this population valuable for finding novel genes involved in MS.

Key Words: familial aggregation • genetically isolated population • multiple sclerosis

Multiple Sclerosis, Vol. 13, No. 1, 17-24 (2007)
DOI: 10.1177/1352458506071216


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