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Comment & Response
October 2013

High Prevalence and Low Fecundity of Mental Disorders May Reflect Recessive Effects

Author Affiliations
  • 1Centre for Psychiatry, Barts and the London School of Medicine and Dentistry, London, England

Copyright 2013 American Medical Association. All Rights Reserved. Applicable FARS/DFARS Restrictions Apply to Government Use.

JAMA Psychiatry. 2013;70(10):1115. doi:10.1001/jamapsychiatry.2013.214

To the Editor Power and colleagues1 appropriately raise the question of why mental disorders that have substantial genetic contributions to etiology and are associated with low fecundity should continue to be highly prevalent in the face of selection pressure. However, they fail to consider what may be an important explanatory factor, which is that recessively acting effects may contribute to risk. Recessively acting alleles are subjected to relatively little selection pressure, especially when there are many different pathogenic mutations, each individually rare, that can form compound heterozygotes to produce disease. Such alleles can then be cumulatively quite common in the population even without bestowing any marked heterozygous advantage. I have recently discussed these issues with respect to schizophrenia and pointed out that recessive effects are consistent with the observed genetic epidemiology.2