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

Sabine Siegert, Andreas Wolf, David N Cooper, Michael Krawczak and Michael Nothnagel

PLOS ONE, 2015, vol. 10, issue 7, 1-21

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 and OR was studied using real data from the NIH GWAS catalogue of reported phenotype associations of single-nucleotide polymorphisms (SNPs). While rare diseases (prevalence 1, up to 20% of mutations causing a pandemic disease (prevalence 10–20%) had ORs

Date: 2015
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Persistent link: https://EconPapers.repec.org/RePEc:plo:pone00:0132150

DOI: 10.1371/journal.pone.0132150

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