Proc Natl Acad Sci U S A. 2003 Oct 20
Willer CJ, Dyment DA, Risch NJ, Sadovnick AD, Ebers GC, Paty DW, Hashimoto SA, Devonshire V, Hooge J, Oger J, Metz L, Warren S, Hader W, Nelson R, Freedman M, Brunet D, Paulseth J, Rice G, O'Connor P, Duquette P, Lapierre Y, Bouchard JP, Murray TJ, Bhan V, Maxner C, Pryse-Phillips W, Stefanelli M.
Wellcome Trust Centre for Human Genetics, University of Oxford, Roosevelt Drive, Oxford OX3 7BN, United Kingdom; ()Department of Genetics, Stanford University, M-335A, Stanford, CA 94305-5120; ( paragraph sign )Department of Medical Genetics, and Faculty of Medicine (Neurology), University of British Columbia, Vancouver, BC, Canada V6T 2B5.
Size and ascertainment constraints often limit twin studies to concordance comparisons between identical and fraternal twins.
Here we report the final results of a longitudinal, population-based study of twins with multiple sclerosis (MS) in Canada.
Bias was demonstrably minimized, and an estimated 75% of all Canadian MS twin pairs were ascertained, giving a sample sufficiently large (n = 370) to permit additional informative comparisons.
Twinning was not found to affect prevalence, and twins with MS did not differ from nontwins for DR15 allele frequency nor for MS risk to their siblings.
Probandwise concordance rates of 25.3% (SE +/- 4.4) for monozygotic (MZ), 5.4% (+/-2.8) for dizygotic (DZ), and 2.9% (+/-0.6) for their nontwin siblings were found.
MZ twin concordance was in excess of DZ twin concordance.
The excess concordance in MZ was derived primarily from like-sexed female pairs with a probandwise concordance rate of 34 of 100 (34 +/- 5.7%) compared with 3 of 79 (3.8 +/- 2.8%) for female DZ pairs.
We did not demonstrate an MZ/DZ difference in males, although the sample size was small.
We observed a 2-fold increase in risk to DZ twins over nontwin siblings of twins, but the difference was not significant.