Affective Disorders: Evaluation of a Three-Allele Model Accounting
for Clinical Heterogeneity
L.A. Sandkuyl and J. Ott
Genetic Epidemiology , 6(1), 265--269 (1989)
Abstract
The group of major affective disorders is clinically heterogeneous.
In the genetic linkage study of the Old Order Amish [Egeland et al.,
1987] the same disease gene appears to be responsible for the
occurrence in one family of several clinically variant forms of
affective disorders. Apparently other genetic or environmental
factors determine the clinical presentation of this disease gene. We
evaluated a three-allele model where the clinical expression of the
disease allele is determined by the other allele at the same locus.
In the presence of a proposed modifying allele the disease allele is
expressed as major depression, in the presence of the normal
(neutral) allele as bipolar disorder (I or II). We applied this
model in our analysis of the Old Order Amish data. In analysis of
linkage between the locus for affective disorders and two DNA
markers on chromosome 11p, we obtained considerably higher
likelihood values under the three-allele model than under a
comparable two-allele model. Also, lodscores were higher under the
three-allele model, with differences in lodscores between both
models ranging from 0.95 to 1.34.
