Maternal Transmission of Multiple Sclerosis in a Dutch Population

Abstract

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-oforigin 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) (PϽ .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.

No Effect of Birth Weight on the Risk of Multiple Sclerosis

“…Maternal effects have also been reported in avuncular families [4] and a large extended Dutch pedigree [5] . In addition, dizygotic (DZ) twin siblings have a higher risk for MS compared to full siblings from the same sibships [6] .…”

2010 Grand Prize Winner

“…An important example is interleukin-18 (Il-18), which exhibits preferential expression in the female, but not male, mPFC (fi gure, panels C and D). Il-18 has been linked to multiple sclerosis (10), a sexually dimorphic neurological disease that predominates in women and is associated with maternal parent-of-origin effects (11). In the POA of the hypothalamus, we also noted that females have three times the number of genes subject to sex-specifi c parental effects as males.…”

Epigenetics in multiple sclerosis

“…[9][10][11][12][13] This phenomenon, named the parent-of-origin effect, has been observed in several complex diseases. The maternal parent-of-origin effect in MS was also confirmed in the Dutch population, 14 and is suggested to underlie the longitudinal increase in the female to male ratio in MS observed in multiple regions. [15][16][17][18] Although the molecular mechanisms of the parent-of-origin effect are not clear, epigenetic mechanisms such as genome imprinting are most likely to be the cause of this phenomenon.…”