Parental transmission of multiple sclerosis: mother, father, or neither?

A large Canadian population-based study has challenged the presence of the ‘Carter effect’ — differing effects of maternal and paternal inheritance - in the transmission of multiple sclerosis risk. The Carter effect predicts that parents less affected by a disease/trait are more genetically loaded for risk alleles, and therefore transmit these more often to their offspring. Previous studies had concluded that the Carter effect existed in MS. This hypothesis was tested in a population-based Canadian MS cohort of 3,088 nuclear families with one affected parent and a total of 8,401 offspring, of whom 798 had MS. Transmission to daughters and sons from affected mothers and fathers was compared. There was equal transmission of MS from affected fathers and affected mothers (9.4%  vs 9.8%). Stratifying by the gender of affected parent, there were no differences in the female:male sex ratio of affected offspring (2.46% vs 2.41%) or unaffected offspring (0.91% vs 0.95%). “These findings show no evidence for the Carter effect and do not support the hypothesis of polygenic inheritance of multiple sclerosis susceptibility by parent,” the researchers concluded. However, they emphasised how the transmission of risk could occur differently in an affected parent compared to an unaffected parent. This could provide an important clue to the mechanisms of risk transmission. The possibility was suggested by previous studies by the same research group in concordant half-sib pairs and in twins, both demonstrating a significant maternal effect in MS risk. “It has been shown that there has been a steady temporal increase in the female-to-male ratio in MS, suggesting that female risk is more strongly influenced by the environment,” they said....