Amyotrophic lateral sclerosis, heterogeneous susceptibility, trauma, and epidemiology

Epidemiological studies relating antecedent trauma and amyotrophic lateral sclerosis (ALS) demonstrate a contradiction: positive (but poorly structured) retrospective case-control studies and negative (but uninterpretably small) prospective cohort studies. In this report, the equations for the case-control odds ratio and cohort relative risk in populations with heterogeneous susceptibility to ALS are analyzed. The case-control odds ratio and cohort relative risk converge as the proportion of ALS-nonsusceptible individuals in a population increases and the rate of ALS in nonsusceptible individuals decreases. Cohort studies of antecedent trauma and ALS have no significant advantage over case-control studies in populations in which most individuals are relatively nonsusceptible to ALS. Accordingly, the relationship between antecedent trauma and ALS can be addressed by carefully defined case-control studies.