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American Journal of Epidemiology Advance Access originally published online on August 24, 2005
American Journal of Epidemiology 2005 162(8):774-778; doi:10.1093/aje/kwi280
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American Journal of Epidemiology Copyright © 2005 by the Johns Hopkins Bloomberg School of Public Health All rights reserved; printed in U.S.A.

ORIGINAL CONTRIBUTIONS

Familial Risk of Multiple Sclerosis: A Nationwide Cohort Study

Nete Munk Nielsen1, Tine Westergaard1, Klaus Rostgaard1, Morten Frisch1, Henrik Hjalgrim1, Jan Wohlfahrt1, Nils Koch-Henriksen2,3 and Mads Melbye1

1 Department of Epidemiology Research, Danish Epidemiology Science Centre, Statens Serum Institut, Copenhagen, Denmark
2 The Danish Register of Multiple Sclerosis, National University Hospital, Copenhagen, Denmark
3 Department of Neurology, Aarhus University Hospital, Aalborg, Denmark

Correspondence to Dr. Nete Munk Nielsen, Department of Epidemiology Research, Statens Serum Institut, Artillerivej 5, Copenhagen 2300 S, Denmark (e-mail: NMN{at}ssi.dk).

Multiple sclerosis (MS) is known to accumulate within families. The magnitude of the familial risk, however, remains uncertain. Using a nationwide MS register and other national registers, the authors estimated relative and absolute risks of MS in a population-based cohort that included 19,615 first-degree relatives of 8,205 Danish MS patients followed from 1968 to 1997. The ratio of observed to expected numbers of MS cases served as the measure of the relative risk of MS. Lifetime risks of MS in first-degree relatives were estimated as the product of the relative risk and the national lifetime risk of MS. Overall, first-degree relatives had a sevenfold increased risk of MS (relative risk = 7.1, 95% confidence interval: 5.8, 8.8) (n = 90) compared with the background population. By modeling the individual incidence rate of MS as the sum of a familial component and a sporadic risk component, the familial excess lifetime risk was found to be 2.5% (95% confidence interval: 2.0, 3.2) among first-degree relatives of MS patients, irrespective of the gender of the proband and the relative. This percentage should be added to a sporadic absolute risk in the general population of 0.5% in women and 0.3% for men. Spouses of MS patients did not experience an increased risk of MS, suggesting no major role for environmental factors acting in adulthood.

cohort studies; Denmark; family; multiple sclerosis; risk

Abbreviations: CI, confidence interval; MS, multiple sclerosis; RR, relative risk


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