A timing-of-birth effect on multiple sclerosis clinical phenotype.

BACKGROUND: A month-of-birth (MOB) effect has been shown in multiple sclerosis (MS). METHODS: Our chi(2) analyses looked at whether this MOB effect differed by MS phenotype ("bout onset," "primary progressive"). RESULTS: The MOB effect was derived from "bout onset" MS patients (May/November ratio = 1.43; chi(2) = 17.32, df = 1, p = 0.000032). CONCLUSIONS: An unspecified environmental effect in early development can influence both multiple sclerosis susceptibility and phenotype.

Multiple sclerosis in stepsiblings: recurrence risk and ascertainment.

Reports implicating specific transmissible agents in multiple sclerosis (MS) susceptibility continue to appear. We therefore re-evaluated MS risk in 687 step-siblings of 19 746 MS index cases. We found the risk of MS to be indistinguishable from that of the general population after diagnostic verification. These results are coherent with studies of adopted children, half siblings and conjugals, showing no risk attributable to the familial microenvironment. This family based genetic epidemiological approach found no trace of transmissibility other than genetic from one affected individual to another in the high prevalence area of Canada. This adds to existing data showing that the action of environment in influencing MS risk is operative at a population level.

Parent-of-origin effect in multiple sclerosis: observations in half-siblings.

Multiple sclerosis is a complex trait in which occurrence rates in offspring are 20-50-fold greater than in the general population. Parent-of-origin effects have been difficult to screen for, since most cases are sporadic. We have compared recurrence risks in half-siblings with respect to their parent in common. Of the 1567 index cases with half-siblings in multiple sclerosis clinics across Canada, we recorded 3436 half-siblings and 2706 full-siblings. Age-adjusted full-sibling risk was 3.11%. By contrast, half-sibling risk in the same families was significantly lower at 1.89% (chi2 test, p=0.006), but higher than expected if familial risk was simply polygenic. For maternal half-siblings, the risk was 2.35% (34 affected siblings of 1859), and 1.31% for paternal half-siblings (15 of 1577), (p=0.048). The difference in risk suggests a maternal parent-of-origin effect in multiple sclerosis susceptibility.