Linkage analysis between bipolar affective disorder and markers on chromosome X

Since 1969, several classical linkage studies suggested an X-chromosome locus for bipolar affective disorder. However, methods using highly polymorphic DNA markers have provided conflicting evidence for linkage, and an X-chromosomal locus for bipolar disorder remains controversial. More recently, Pekkarinen et al. (1995) found a maximum LOD score of 3.54 at the marker DXS994 in a large bipolar Finnish kindred. In the present study, we attempted to replicate this finding using 43 families multiply affected by bipolar affective disorder. These families were selected for the absence of male-to-male transmission of the disease, and were genotyped for two microsatellte markers, DXS1227 and DXS1062 (which is about 2 cM telomeric to DXS994). Linkage to this region was excluded either using a two-point lod score method with two plausible genetic models, or by a model-free lod score analysis which does not require specification of a particular mode of transmission. We conclude that there is no evidence of a common major gene for bipolar affective disorder at Xq25-q27 in our set of families.