Young Scientific Investigators’ Session 2Wednesday, October 02, 2013, 16:00 - 16:12
Modest familial risks for multiple sclerosis: a population-based registry study of SwedenH. Westerlind, R. Ramanujam, D. Uvehag, R. Kuja-Halkola, M. Boman, P. Lichtenstein, J. Hillert (Solna, SE)
In contrast to most previous studies of familial risks of multiple sclerosis (MS), we used national registries to assess the recurrence of disease. Through the Swedish Multiple Sclerosis registry and a nationwide hospital in patient registry, a total of 28,191 patients with MS were identified. We used the national multi-generation registry to identify first and second degree relatives and cousins, and the Swedish Twin Registry to identify twins and zygosity information. Crude and age corrected risks were calculated. Relative risks for MS were obtained by comparison with controls and their relatives matched for gender and year of birth.
In general, lower risks than previously reported for MS were observed. Thus, we observed age adjusted risks for monozygotic twins (n=78) of 17.28%, for dizygotic twins (n=237) 1.82%, siblings 2.55%, parent-child 2.03%, maternal half siblings 1.68%, paternal half siblings 1.40%, grandparents 0.28%, avuncular pairs 1.00% and cousins 0.57%.
The relative risks for monozygotic twins were 16.53, dizygotic twins 2.78 (non-significant (n.s.)), siblings 8.11, parent-child 5.51, maternal half siblings 5.26, paternal half siblings 7.21, grandparents 1.68 (n.s.), avuncular pairs 2.81 (n.s.) and cousins 2.44.
Surprisingly, despite a well-established lower prevalence of MS in males, relative risks were most often higher for paternal relations, signifying higher transmission to offspring from the lower prevalent sex, known as the Carter effect.
Among 497 first degree relatives by adoption, two with MS were identified, corresponding to an age adjusted risk of 0.67% or a relative risk of 2.44 (n.s.) over that of controls. Sixty-five adopted siblings to MS patients were identified, and one of these was affected (n.s.).
We estimated the heritability of MS using 74,757 twin pairs with known zygosity, where of 315 were affected with MS, and adding information on 2.5 million sib pairs to increase power. The heritability, h2, was estimated to be 0.64 (0.36-0.76). The shared environmental component was estimated to be 0.07 (0.00 – 0.18), which is in line with previously published data.
Comparisons with previous estimations of prevalence of MS patients and number of twins indicate that we obtained coverage of 95.9 % of the Swedish MS population, arguing for the validity of the findings. In summary, whereas MS is to a great extent an inherited trait, the overall risks may be lower than previously reported.
HW has nothing to disclose, source of funding is Karolinska Institutet.
RR has nothing to disclose, sources of funding are the Karolinska Instituets stifelse and the Swedish Research Council.
DU has nothing to disclose.
RKH has nothing to disclose, sources of funding is Karolinska Institutet and the Swedish prison and probation agency.
MB has nothing to disclose.
PL has nothing to disclose.
JH received honoraria for serving on advisory boards for BiogenIdec, Merck-Serono and Novartis and for speaker’s fees from BiogenIdec, Merck-Serono, Bayer-Schering, Teva and Sanofi-Aventis. He has served as P.I. for and received projects supported by BiogenIdec, Merck-Serono, and Bayer-Schering. His MS research is funded by the Swedish Research Council, Bibbi and Nils Jensens Foundation and the European Commission.