Progress and pitfalls: bipolar molecular linkage studies.

This paper reviews the history of molecular genetic linkage studies of bipolar disorder. The topic is introduced with a brief discussion of various genetic concepts, including linkage, lod scores and non-parametric statistics. It is emphasized that criteria for declaring linkage must include independent confirmation by a second group of investigators. Given that the inherited susceptibility for bipolar disorder is most likely explained by multiple genes of small effect, simulations indicate that universal confirmation of valid linkages cannot be expected. With this background, several valid linkages of BP disorder to genomic regions are reviewed. These valid linkages include 18p11, 18q22, 21q21, Xq26 and 4pter. The issue of anticipation and expanding triplet repeats is discussed. Finally, there is a brief section on recommendations for future genetic linkage studies of bipolar disorder.