The genetic implications of age-dependent penetrance in manic-depressive illness

Abstract

An age dependent penetrance function was derived for manic-depressive illness, using age-of-onset data from sixty-one affected probands. The function used was a one-hit model, with earliest age-of-onset at about 14 yr, and a steadily increasing probability of manifesting the illness thereafter. The utility of the penetrance function for pedigree analysis was illustrated, using the families of the sixty-one probands. A sex-linked dominant model of inheritance was about eighty-nine times more likely than an autosomal dominant model, and both were far more likely than autosomal recessive or sex-linked recessive models. The more general single major locus model and the polygenic model cannot be ruled out, but would seem to be unnecessarily over-parameterized for the data at hand. The sex-linked dominant and autosomal dominant models were also compared, by means of the age specific morbidity risks and sibs and children. Both models provided a fairly close fit of expectation and observation, but the sex-linked model was preferable. Although the genetic conclusions cannot automatically be applied to other material, the analytical techniques should be useful elsewhere. Other uses of the penetrance function were indicated.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/23042/1/0000614.pd

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