title: Linkage analysis in bipolar pedigrees adds support for a susceptibility locus on 21q22.
abstract: Several studies provide suggestive evidence of a susceptibility locus for bipolar disorder at chromosome 21q22-23. In an attempt to replicate these findings, we have analyzed linkage to 11 polymorphic markers from this region in 18 Bulgarian pedigrees with affective disorder. Two-point linkage analysis under assumption of homogeneity and a dominant model with reduced penetrance produced modest positive values for some of the markers tested under a 'narrow' phenotype definition, including bipolar I and II, and schizoaffective disorder. The maximum two-point score (lod=1.76, theta=0.00) was at marker D21S1919. Non-parametric linkage analysis under the same phenotype model, yielded positive NPLall values (P<0.05) over the region between markers D21S211 and D21S416, with a peak at D21S1252 (NPL Zall=2.32, P=0.0003). The multipoint lod score (GENEHUNTER) reached a suggestive value for linkage (lod=2.10) also at marker D21S1252. The results under a recessive model were completely negative. These data add to the evidence for the existence of a susceptibility locus for bipolar affective disorder on chromosome 21q22.
authors.affiliation: Laboratory of Molecular Pathology, University Hospital of Obstetrics, Medical University Sofia, Bulgaria. kaneva@medfac.acad.bg
authors.forename: Radka P
authors.initials: RP
authors.lastname: Kaneva
authors.forename: Vesselin M
authors.initials: VM
authors.lastname: Chorbov
authors.forename: Vihra K
authors.initials: VK
authors.lastname: Milanova
authors.forename: Christian S
authors.initials: CS
authors.lastname: Kostov
authors.forename: Kaloian I
authors.initials: KI
authors.lastname: Nickolov
authors.forename: Christina F
authors.initials: CF
authors.lastname: Chakarova
authors.forename: Vesela S
authors.initials: VS
authors.lastname: Stoyanova
authors.forename: Amelia N
authors.initials: AN
authors.lastname: Nikolova-Hill
authors.forename: Stefan K
authors.initials: SK
authors.lastname: Krastev
authors.forename: George N
authors.initials: GN
authors.lastname: Onchev
authors.forename: Ivo M
authors.initials: IM
authors.lastname: Kremensky
authors.forename: Luba V
authors.initials: LV
authors.lastname: Kalaydjieva
authors.forename: Assen V
authors.initials: AV
authors.lastname: Jablensky
mesh_terms: D001714:Bipolar Disorder / Q000235:genetics*; D002031:Bulgaria; D002170:Canada; D002874:Chromosome Mapping; D002891:Chromosomes, Human, Pair 21 / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006801:Humans; D007585:Jews; D008126:Lod Score; D008297:Male; D008957:Models, Genetic; D010375:Pedigree; D014481:United States