A population‐based study of multiple sclerosis in twins: Update

Abstract

This study is a 7.5-year follow-up of a population-based series of twins with multiple sclerosis (MS) whose mean age now exceeds 50 years. The twin pairs were identified through the Canadian nationwide system of MS clinics and were drawn from a population of 5,463 patients. After 7.5 years, the monozygotic concordance rate increased from 25.9 to 30.8% and the dizygotic-like sex concordance rate from 2.4 to 4.7%. These results are very similar to those of other population-based studies and to our own modified replication twin data reported here. We interpret the data to mean that MS susceptibility is genetically influenced, and a single dominant or even a single recessive gene is unlikely to account for this effect. The difference in concordance rates suggests that at least two or more genes are operative. These data also have important implications for the nature of the environmental effect(s) in MS susceptibility. Most monozygotic twins are discordant even after a correction for age and magnetic resonance imaging findings. This unambiguously demonstrates the powerful effect of nonheritable factors.

Multiple sclerosis genetics: leaving no stone unturned

“…13 Concordant sibs tend to share age of symptom onset rather than year of onset, and second and third degree relatives of MS patients are also at an increased risk. Furthermore, twin studies from different populations consistently indicate pairwise concordance (20-40% in identical twin pairs compared to 2-5% in like-sex fraternal twin pairs) providing additional evidence for a genetic etiology in MS. 14,15 Interestingly, twin concordance appears to exhibit, at least in the Canadian series, gender dimorphism. 16 Finally, parent-of-origin effects may also influence both disease susceptibility and outcome, [17][18][19] and concordance in families for early and late clinical features has been observed as well, suggesting that in addition to susceptibility, genes may influence disease severity or other aspects of the clinical phenotype.…”

Allelic association of sequence variants in the herpes virus entry mediator-B gene (PVRL2) with the severity of multiple sclerosis

“…In Caucasian populations, 20-40% of patients have a benign disease course over extended periods of time, 50% enter a secondary-progressive phase after about 5-15 years from disease onset, and the remaining 10-30% of patients are diagnosed with primary progressive MS. 2,3 A very small proportion of patients presents with a progressiverelapsing form of the disorder. A large body of research supports genetic influences on both susceptibility to, and progression of, MS. [4][5][6] However, the relationship between genotype and phenotype is clearly complex, and a number of different polymorphic genes with individually small or moderate effects are believed to act together or independently to increase the risk of being affected with MS, or to exacerbate the course of the disease.…”

Genome-wide TDT analysis in a localized population with a high prevalence of multiple sclerosis indicates the importance of a region on chromosome 14q

“…Epidemiological studies show that multiple sclerosis (MS) has a substantial genetic component, 3,4 but only HLA genes have so far been confirmed to be of importance. 5,6 Extensive efforts in linkage analysis have failed to provide more than a number of uncertain and vaguely delineated loci, probably since several genes with moderate effects influence the disease susceptibility.…”