Recurrence risks in the presence of single gene susceptibility to environmental agents

M. J. Khoury, T. H. Beaty

Research output: Contribution to journalArticlepeer-review

5 Scopus citations


Investigators often attribute the 2-5% sibling recurrence risks of common congenital malformations to a multifactional/threshold model (MFT) mechanism. However, most studies fail to address adequately the role of specific environmental factors and their interaction with genetic factors in recurrence risks. We consider the effects of a hypothetical environmental agent on recurrence risks in the presence of a single gene-mediated differential susceptibility. It can be shown that recurrence risks increase with increasing population exposure frequency to the agent and the strength of gene-environment interaction (relative risk among susceptible genotypes). However, they are usually much lower than expected on the basis of simple Mendelian segregation. Moreover, recurrence risks decline considerably between 1st, 2nd, and 3rd degree relatives, especially for recessive traits. Because single gene-mediated differential susceptibility can mimic the MFT model in many instances, family studies of malformations (and other common diseases) could be more rewarding if they incorporate in their design and analyses specific environmental exposures affecting disease risk.

Original languageEnglish (US)
Pages (from-to)159-169
Number of pages11
JournalAmerican journal of medical genetics
Issue number1
StatePublished - 1987

ASJC Scopus subject areas

  • Genetics(clinical)


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