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American Journal of Epidemiology Advance Access originally published online on June 22, 2009
American Journal of Epidemiology 2009 170(3):289-296; doi:10.1093/aje/kwp143
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American Journal of Epidemiology © 2009 The Authors
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/2.0/uk/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

ORIGINAL CONTRIBUTIONS

Age of Onset in Concordant Twins and Other Relative Pairs With Multiple Sclerosis

A. Dessa Sadovnick, Irene M. Yee, Colleen Guimond, Jacques Reis, David A. Dyment and George C. Ebers

Correspondence to Dr. A. Dessa Sadovnick, Department of Medical Genetics, Vancouver Coastal Health Authority–University of British Columbia Hospital, G-920 Detwiller Pavilion, Vancouver, British Columbia V6T 2B5, Canada (e-mail: sadovnik{at}infinet.net).

Received for publication October 17, 2008. Accepted for publication April 24, 2009.

The ages of onset in multiple sclerosis cases span more than 7 decades. Data are presented for affected relative pairs from a Canadian population base of 30,000 multiple sclerosis index cases (1993–2008). The effects of genetic sharing, parent of origin, intergenerational versus collinear differences, and gender on the ages of onset were evaluated in the following concordant pairs: monozygotic twins (n = 29), dizygotic twins (n = 10), siblings (n = 614), first cousins (n = 405), half siblings (n = 29), parent/child (n = 285), and aunt/uncle/niece/nephew (avunculars) (n = 289). Fisher's z test assessed intraclass correlation (r) for ages of onset. Correlations for monozygotic twins, dizygotic twins, full siblings, and first cousins were 0.60, 0.54, 0.20, and 0.10, respectively. Dizygotic twins resembled monozygotic twins more than siblings. The age-of-onset correlation for maternal half siblings (r = 0.37) was higher than that for paternal half siblings (r = 0.26), consistent with other observations suggesting an intrauterine environmental effect on multiple sclerosis risk. Intergenerational comparisons are complicated by substantial increases of multiple sclerosis incidence over time. Genetic loading (familial vs. sporadic cases) did not generally influence the age of onset, but correlation of age of onset in multiple sclerosis relative pairs was proportional to genetic sharing. A maternal parent-of-origin effect on the age of onset in collinear generations was suggested.

age of onset; environment; family; genetics; multiple sclerosis; twins

Abbreviations: CCPGSMS, Canadian Collaborative Project on Genetic Susceptibility to Multiple Sclerosis; SD, standard deviation


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