Mutations Causing Complex Disease May under Certain Circumstances Be Protective in an Epidemiological Sense.

ABSTRACT: Guided by the practice of classical epidemiology, research into the genetic basis of complex disease has usually taken for granted the dictum that causative mutations are invariably over-represented among clinically affected as compared to unaffected individuals. However, we show that this supposition is not true and that a mutation contributing to the etiology of a complex disease can, under certain circumstances, be depleted among patients. Populations with defined disease prevalence were repeatedly simulated under a Wright-Fisher model, assuming various types of population history and genotype-phenotype relationship. For each simulation, the resulting mutation-specific population frequencies and odds ratios (ORs) were evaluated. In addition, the relationship between mutation frequency a

SUBMITTER: Siegert S 

PROVIDER: S-EPMC4498598 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature