title: Genome scan of pedigrees multiply affected with bipolar disorder provides further support for the presence of a susceptibility locus on chromosome 12q23-q24, and suggests the presence of additional loci on 1p and 1q.
abstract: OBJECTIVE
  To localize genes conferring susceptibility to bipolar affective disorder.
  
  
  METHODS
  Seven families were selected on the basis of containing multiple cases of bipolar affective disorder present in three or more generations, an absence of schizophrenia and unilineal transmission. DNA samples from these families were genotyped with 365 microsatellite markers spaced at approximately 10 cM intervals across the whole genome. All markers were subjected to initial two-point and three-point analyses using LOD score and model-free analysis. All regions producing a result significant at P<0.01 were then subjected to four-point LOD score analysis under the assumption of heterogeneity. RESULTSA four-point LOD score of 2.8 was obtained using a dominant model and including unipolar cases as affected in the region of D12S342. Four-point LOD scores of 2 were obtained around D1S243, D1S251 and D3S1265. The positive results around D1S243 were accounted for by a LOD score of 3.1 occurring in a single pedigree.
  
  
  CONCLUSIONS
  Since there has been previous strong support for linkage to the region of 12q23-q24 around D12S342, it now seems very probable that it does indeed contain a gene influencing susceptibility to bipolar affective disorder. Some evidence for linkage in the region of 1q near to D1S251 has been reported in one previous study. It therefore seems that this region of 1q and the region of 1p close to D1S243 may also harbour susceptibility genes.
authors.affiliation: Joint Academic Department of Psychological Medicine, St Bartholomew's and Royal London School of Medicine and Dentistry, London, UK. dcutis@hgmp.mrc.ac.uk
authors.forename: David
authors.initials: D
authors.lastname: Curtis
authors.forename: Gursharan
authors.initials: G
authors.lastname: Kalsi
authors.forename: Jon
authors.initials: J
authors.lastname: Brynjolfsson
authors.forename: Melvin
authors.initials: M
authors.lastname: McInnis
authors.forename: Jane
authors.initials: J
authors.lastname: O'Neill
authors.forename: Ciaran
authors.initials: C
authors.lastname: Smyth
authors.forename: Eamonn
authors.initials: E
authors.lastname: Moloney
authors.forename: Patrice
authors.initials: P
authors.lastname: Murphy
authors.forename: Andrew
authors.initials: A
authors.lastname: McQuillin
authors.forename: Hannes
authors.initials: H
authors.lastname: Petursson
authors.forename: Hugh
authors.initials: H
authors.lastname: Gurling
mesh_terms: D001714:Bipolar Disorder / Q000235:genetics*; D002874:Chromosome Mapping; D002878:Chromosomes, Human, Pair 1; D002881:Chromosomes, Human, Pair 12; D005260:Female; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D015894:Genome, Human; D006801:Humans; D008126:Lod Score; D008297:Male; D010375:Pedigree
chemical_list: D005819:Genetic Markers