There is more than one way to collect data for linkage analysis. What a study of epilepsy can tell us about linkage strategy for psychiatric disease
D. A. Greenberg
Department of Psychiatry, Mount Sinai Medical Center, New York, NY 10029-6574.
The most popular strategy for finding genes in psychiatric diseases has
been to focus on large pedigrees with many affected members. While this
strategy has sound advantages, it also has drawbacks that have seldom been
addressed. The strategy of using smaller families also has its place in a
linkage analysis. To illustrate the point, I discuss herein the successful
search for a gene for another common complex disease, namely, idiopathic
primary generalized epilepsy. There, investigators in the Los Angeles
(Calif) Epilepsy Program used mostly nuclear families who were chosen
through a proband with highly specific characteristics. An independent
study, using a different strategy but one still focused on small families,
then confirmed the linkage. However, investigators of both epilepsy
projects put much care into determining which clinical characteristics
would be used to define the index cases. The implications for the study of
psychiatric disease are as follows: (1) careful attention must be paid to
clinical presentation, and (2) there is room for both large-pedigree and
small-family strategies in designing linkage studies.
