Linkage analysis of manic depression (bipolar affective disorder) in Icelandic and British kindreds using markers on the short arm of chromosome 18.

Attempts were made to follow up results of a previous linkage study which suggested that a locus-modifying susceptibility to bipolar and related unipolar affective disorder might be present in the pericentromeric region of the short arm of chromosome 18. Twenty-three multiply affected pedigrees collected from Iceland and the UK were genotyped using three highly polymorphic microsatellite markers at D18S37, D18S40 and D18S44 which span the region implicated. Lod score analyses under the assumption of heterogeneity and non-parametric linkage analyses were performed. The total lod scores obtained were strongly negative, and analysis allowing for heterogeneity did not suggest that any subgroup of the families was linked. Model-free linkage analysis using extended relative pair analysis and MFLINK also failed to detect any evidence for linkage. Our study provides no support for the presence of a locus-modifying genetic susceptibility to bipolar affective disorder in the pericentromeric region of chromosome 18q11. Further analyses in independent samples should help to reveal whether our negative results are due to locus heterogeneity or whether the original results were false-positive.