title: Parental transmission of MS in a population-based Canadian cohort.
abstract: OBJECTIVE
  Genetic and environmental factors have important roles in multiple sclerosis (MS) susceptibility. The precise nature of these factors and mode of inheritance remains unknown. A female predominance is universally found. Recently, offspring of affected fathers were reported to be more likely to have MS than those of affected mothers. This was attributed to the Carter effect, which is seen in polygenic disorders. The Carter effect predicts that affected parents of the sex lesser affected by a disease/trait are more genetically loaded for risk alleles and thus transmit these more often to their offspring. This hypothesis was tested in a population-based Canadian MS cohort.
  
  
  METHODS
  Using the longitudinal Canadian database, we identified 3,088 nuclear families with one affected parent and a total of 8,401 offspring, of which 798 had MS. Transmission to daughters and sons from affected mothers and fathers was compared.
  
  
  RESULTS
  There was equal transmission of MS from affected fathers vs affected mothers (9.41% vs 9.76%). Stratifying by gender of affected parent there were no differences in the female:male sex ratio of affected (2.46% vs 2.41%, p = 0.88) or unaffected offspring (0.91% vs 0.95%, p = 0.46).
  
  
  CONCLUSIONS
  We observed equal disease transmission to offspring from affected mothers and affected fathers, no difference in the female:male sex ratio of affected offspring, and previously no difference in sibling recurrence risk by gender of parent affected. These findings show no evidence for the Carter effect and do not support the hypothesis of polygenic inheritance of multiple sclerosis susceptibility by parent.
authors.affiliation: Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK.
authors.forename: B M
authors.initials: BM
authors.lastname: Herrera
authors.forename: S V
authors.initials: SV
authors.lastname: Ramagopalan
authors.forename: S
authors.initials: S
authors.lastname: Orton
authors.forename: M J
authors.initials: MJ
authors.lastname: Chao
authors.forename: I M
authors.initials: IM
authors.lastname: Yee
authors.forename: A D
authors.initials: AD
authors.lastname: Sadovnick
authors.forename: G C
authors.initials: GC
authors.lastname: Ebers
mesh_terms: D002170:Canada / Q000453:epidemiology; D015331:Cohort Studies; D005260:Female; D040741:Genetic Load; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006801:Humans; D040582:Inheritance Patterns / Q000235:genetics*; D008137:Longitudinal Studies; D008297:Male; D020412:Multifactorial Inheritance / Q000235:genetics; D009103:Multiple Sclerosis / Q000453:epidemiology / Q000235:genetics*; D010375:Pedigree; D012307:Risk Factors; D012727:Sex Characteristics