Progress and pitfalls: bipolar molecular linkage studies

This paper reviews the history of molecular genetic linkage studies of bipo lar disorder. The topic is introduced with a brief discussion of various ge netic concepts, including linkage, lod scores and non-parametric statistics . It is emphasized that criteria for declaring linkage must include indepen dent confirmation by a second group of investigators. Given that the inheri ted susceptibility for bipolar disorder is most likely explained by multipl e genes of small effect, simulations indicate that universal confirmation o f valid linkages cannot be expected. With this background, several valid li nkages 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. (C) 1998 Elsevier Science B.V. All rights reserved.