A LINKAGE STUDY OF DISTAL CHROMOSOME 5Q AND BIPOLAR DISORDER

There are well-established abnormalities of hypothalamic-pituitary-adr enal (HPA) axis and beta 2 adrenergic receptor function in affective d isorders. The genes for the glucocorticoid receptor (GRL) and the beta 2 adrenergic receptor (ADRB2) have been cloned and mapped to distal c hromosome 5q. In this study, we have examined polymorphisms of these t wo candidate genes and other nearby markers for linkage to bipolar dis order in Amish pedigree 110 and three large Icelandic pedigrees. These loci were tested for linkage in two-point and multipoint analyses usi ng a model of autosomal dominant transmission with age-dependent reduc ed penetrance. Two-point analyses revealed a maximum LOD score of 1.14 at theta=0.20 from GRL. Linkage could be excluded to ADRB2 as well as to three nearby anonymous markers, D5S207, D5S70, and D5S119. Analyse s of another anonymous marker, D5S36, were inconclusive. Multipoint an alyses excluded linkage to a 55 cM region including the interval betwe en D5S207 and D5S36 and flanking regions, with the exception of a 7 cM interval between GRL and ADRB2. Despite the intriguing positive LOD s core obtained with GRL, linkage to bipolar disorder could not be demon strated in the region examined.