OBJECTIVE: To investigate the parental relationship of patients with multiple sclerosis (MS) from an extended pedigree with extensive genealogical information up to the middle of the 18th century. DESIGN: Multiple sclerosis is a complex disease resulting from genetic and environmental factors. Parent-of-origin effect, a phenomenon when the same allele may express differently depending on the sex of the transmitting parent, may influence the risk for MS. We investigated parental relationships between patients with MS using extensive genealogical information available from the Genetic Research in Isolated Populations program. We compared the average kinship of the parents of MS patients. We further explored the distribution of shortest genealogical links between parents of MS patients. Subjects Twenty-four MS patients from the isolated population who could be linked within a large complex pedigree, including 2471 people in total. RESULTS: The results consistently indicate a higher prevalence of maternal transmission of MS. The kinship between mothers of patients was 3.8 times higher than that between fathers (bootstrap P = .01). Among the 814 shortest connections between parents, 333 were maternal (40.9%, vs 25.0% expected), 98 were paternal (12.0%, vs 25.0% expected), and 383 were maternal-paternal (47.1%, vs 50.0% expected) (P < .001). CONCLUSIONS: Mothers of MS patients were more closely related than their fathers. This skewed relationship shows evidence for a maternal effect in MS. The most likely explanation is a gene-environment effect that takes place in utero.
OBJECTIVE: To investigate the parental relationship of patients with multiple sclerosis (MS) from an extended pedigree with extensive genealogical information up to the middle of the 18th century. DESIGN:Multiple sclerosis is a complex disease resulting from genetic and environmental factors. Parent-of-origin effect, a phenomenon when the same allele may express differently depending on the sex of the transmitting parent, may influence the risk for MS. We investigated parental relationships between patients with MS using extensive genealogical information available from the Genetic Research in Isolated Populations program. We compared the average kinship of the parents of MSpatients. We further explored the distribution of shortest genealogical links between parents of MSpatients. Subjects Twenty-four MSpatients from the isolated population who could be linked within a large complex pedigree, including 2471 people in total. RESULTS: The results consistently indicate a higher prevalence of maternal transmission of MS. The kinship between mothers of patients was 3.8 times higher than that between fathers (bootstrap P = .01). Among the 814 shortest connections between parents, 333 were maternal (40.9%, vs 25.0% expected), 98 were paternal (12.0%, vs 25.0% expected), and 383 were maternal-paternal (47.1%, vs 50.0% expected) (P < .001). CONCLUSIONS: Mothers of MSpatients were more closely related than their fathers. This skewed relationship shows evidence for a maternal effect in MS. The most likely explanation is a gene-environment effect that takes place in utero.
Authors: Eric J Kildebeck; Ram Narayan; Avindra Nath; Howard Weiner; Shin Beh; Peter A Calabresi; Lawrence Steinman; Eugene O Major; Teresa C Frohman; Elliot M Frohman Journal: J Neurol Date: 2016-10-12 Impact factor: 4.849
Authors: Sreeram V Ramagopalan; Colleen Guimond; Maria Criscuoli; David A Dyment; Sarah-Michelle Orton; Irene M Yee; George C Ebers; Dessa Sadovnick Journal: BMC Neurol Date: 2010-11-16 Impact factor: 2.474
Authors: S V Ramagopalan; I M Yee; D A Dyment; S-M Orton; R A Marrie; A D Sadovnick; G C Ebers Journal: Neurology Date: 2009-06-10 Impact factor: 9.910
Authors: I A Ketelslegers; C E Catsman-Berrevoets; R F Neuteboom; M Boon; K G J van Dijk; M J Eikelenboom; R H J M Gooskens; E H Niks; W C G Overweg-Plandsoen; E A J Peeters; C M P C D Peeters-Scholte; B T Poll-The; J F de Rijk-van Andel; J P A Samijn; I N Snoeck; H Stroink; R J Vermeulen; A Verrips; J S H Vles; M A A P Willemsen; R Rodrigues Pereira; R Q Hintzen Journal: J Neurol Date: 2012-02-17 Impact factor: 4.849
Authors: Sreeram V Ramagopalan; William Valdar; David A Dyment; Gabriele C DeLuca; Sarah-Michelle Orton; Irene M Yee; Maria Criscuoli; George C Ebers; A Dessa Sadovnick Journal: BMC Neurol Date: 2008-08-01 Impact factor: 2.474