Penetrance in the presence of genetic susceptibility to environmental factors

M. J. Khoury, W. D. Flanders, T. H. Beaty

Research output: Contribution to journalArticlepeer-review

9 Scopus citations


Many single-gene disorders (especially dominant traits) are known to exhibit 'incomplete penetrance', a term often criticized as reflecting our ignorance of genetic and environmental factors that may interact with the genotype to determine the ultimate phenotype of the individual. We explore the effects of an environmental factor on penetrance for a simple model of single gene-mediated susceptibility to environmental factors. We show that penetrance of the susceptibility genotype increases with increasing frequency of exposure to the factor and the strength of interaction between the factor and the genotype (relative risk). For disorders with disease frequency of 0.001 or less (as seen with many congenital malformations), penetrance is generally low (<10%) if the exposure frequency is low (<10%) even in the face of strong gene-environment interaction. Such low penetrance can lead to low recurrence risks. Single-gene effects could easily be overlooked in genetic analysis unless specific environmental factors are considered.

Original languageEnglish (US)
Pages (from-to)397-403
Number of pages7
JournalAmerican journal of medical genetics
Issue number2
StatePublished - 1988

ASJC Scopus subject areas

  • Genetics(clinical)


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