title: Anticipation of age at onset in multiple sclerosis: methodologic pitfalls.
abstract: OBJECTIVE
  There are several reports that claim anticipation in complex or polygenic diseases such as multiple sclerosis (MS), Crohn disease or schizophrenia. The aim of the present study was to assess age at onset of MS during the last 60 years in the region of Costa de Ponent (Barcelona, Spain) showing how apparent changes in age at onset between generations can be an artefact of analysis based on cohorts that have not been followed enough time.
  
  
  METHODS
  The study comprised 1100 patients diagnosed of MS. The method used to correct for follow-up time bias involves constructing comparison cohorts that had been observed for the same amount of time. To ensure equal follow-up times, we restricted our analysis to patients whose onset was by 37 years of age (percentile 75) and were at least 37 years old. We analysed differences in age at onset using log-rank test to compare survival curves estimated by Kaplan-Meier method.
  
  
  RESULTS
  Age at onset decreases progressively from older to younger generations. However, when adjustment to equal follow-up time was done, anticipation in age at onset was not found.
  
  
  CONCLUSIONS
  Anticipation of age at onset is undetectable when adjusted for follow-up time.
authors.affiliation: Neurology Department, Malmö University Hospital, Sweden.
authors.forename: L
authors.initials: L
authors.lastname: Alonso-Magdalena
authors.forename: L
authors.initials: L
authors.lastname: Romero-Pinel
authors.forename: E
authors.initials: E
authors.lastname: Moral
authors.forename: O
authors.initials: O
authors.lastname: Carmona
authors.forename: L
authors.initials: L
authors.lastname: Gubieras
authors.forename: J M
authors.initials: JM
authors.lastname: Ramón
authors.forename: S
authors.initials: S
authors.lastname: Martínez-Yélamos
authors.forename: T
authors.initials: T
authors.lastname: Arbizu
mesh_terms: D000367:Age Factors; D017668:Age of Onset; D000375:Aging / Q000235:genetics*; D020132:Anticipation, Genetic; D015982:Bias; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D009103:Multiple Sclerosis / Q000235:genetics* / Q000401:mortality; D016019:Survival Analysis; D013997:Time Factors