Lithium responsive bipolar disorder, unilineality, and chromosome 18: A linkage study

Over the last three years several studies have investigated the hypothesis of linkage between bipolar disorder and markers on chromosome 18, Although independent groups have reported positive results, it is still not clear ho w these should be interpreted, as linkage spans a considerably large segmen t of the chromosome. In this study we have investigated linkage with chromo some 18 markers in 19 families of lithium-responsive bipolar patients, as a way to select a more homogeneous population. In addition, we have investig ated whether there is evidence of a parent-of-origin effect as suggested by previous studies. Eleven markers spanning the whole chromosome were typed and linkage analysis was carried out using parametric and nonparametric met hods. Analysis of the whole sample provided nonsignificant linkage results. However, when the sample included only unilineal families, and was further stratified according to parental origin, two chromosomal regions provided modestly positive lod scores. Maximum lod scores of 1.04 (P = 0.001) at D18 S53 and 0.87 (P = 0.045) at D18S61 were observed for maternal and paternal pedigrees, respectively Nonparametric analysis yielded similar results, In conclusion, our results are congruent with previous reports that suggest an advantage of unilineal pedigrees in linkage analysis of bipolar disorder a nd cannot rule out a parent-of-origin effect in this genomic region. Am. J, Med, Genet, (Neuropsychiatr. Genet,) 88:411-415, 1999, (C) 1999 Wiley-Liss , Inc.