Support for the possible locus on chromosome 4p16 for bipolar affective disorder

Significant evidence for linkage between bipolar affective disorder and markers on chromosome 4p16 has been reported in Scottish families. Linkage analyses using 16 DNA markers covering more than 50 cM from chromosome 4pter-4p12, including candidate genes encoding the dopamine D5 receptor and an adrenergic receptor (2C), were performed in two Danish families with bipolar affective disorder. Assuming homogeneity in the two families, the highest lod score found in the two-point linkage analyses was 2.00 at 0.03 recombination fraction for D4S394, i.e. the marker which also was most significant in the original Scottish study. Simulation showed that such a lod score would only occur six out of 10,000 times with an unlinked marker. Though the present study thus replicates the Scottish findings according to the criteria suggested by Lander and Kruglyak, caution is warranted as the mode of inheritance which yielded the highest lod score in the two studies was different. Final proof of a disease locus in the Scottish and our study has to await the identification of a DNA sequence of functional significance for bipolar disorder.