Disease classification and transmission effects on linkage analyses in the NIMH1 bipolar disorder pedigrees

In this analysis of bipolar affective disorder, 22 families from the NIMH1 data set were further grouped into three transmission patterns: male to male, male to female, and maternal. The data were analyzed under three classifications of affection status: Bipolar I (BPI) only, BPI and Bipolar II (BPII), and BPI, BPII, and recurrent unipolar. LINKAGE was run on each of the subsets, and SIBPAL was run on the full and grouped data sets. A lod score of 1.09 was found for marker D18S62 in the maternal subset, when classifying affecteds as BPI, BPII, or recurrent unipolar. Affected sib-pair analysis showed evidence for linkage with markers D18S62, D18S37, D18S53, D18S40, D18S45, and D18S56 in the male to male transmission groups and the full data set. Linkage was not consistently found in the maternal and father/daughter groups. These results indicate that subsetting by parental transmission may result in less heterogeneity and have significant effects on linkage findings. Studies using a broader definition of affection status may provide considerably more information for linkage.