title: A linkage study of bipolar illness.
abstract: BACKGROUND
  Although genetic epidemiological studies of bipolar (BP) illness are consistent with a heritable component, inherited risk factors remain unknown. The goal of the present study is to describe the localization of BP susceptibility loci through linkage strategies, including a genome-wide search.
  
  
  METHODS
  A linkage study of 22 BP families has been performed. These BP families include almost 400 persons, 173 of whom have been diagnosed as having BP I, schizoaffective, BP II with major depression, or recurrent unipolar illness. Using an autosomal dominant disease model with 85% or 50% age-dependent penetrance, and a recessive model with 85% penetrance, linkage analyses were performed assuming a narrow (BP and schizoaffective) or a broad (BP, schizoaffective, or unipolar) definition of the BP spectrum. Affected sibling pairs and affected pedigree member analyses were performed when positive lod scores were observed in multiple pedigrees. The present article describes linkage analysis of 310 DNA markers on chromosomes 1, 5p, 6, 8, 10q, 11q, and 12 to 18.
  
  
  RESULTS
  None of the loci examined disclosed compelling evidence for linkage using lod score analyses. Model-independent analysis by multilocus affected pedigree member method in the pericentromeric chromosome 18 region disclosed statistically significant evidence (P < .0001) for a BP susceptibility gene in this region. Multilocus analysis by affected sibling pair method also disclosed evidence for linkage (P < .00008).
  
  
  CONCLUSIONS
  Our results imply that a BP susceptibility gene exists near the centromere of chromosome 18. Confirmation of this finding (by independent investigators studying different pedigrees) has been published, suggesting that a valid BP disease linkage may have been discovered.
authors.affiliation: Department of Psychiatry and Human Behavior, Jefferson Medical College, Thomas Jefferson University, Philadelphia, Pa, USA. berrettiniw@jeflin.tju.edu
authors.forename: W H
authors.initials: WH
authors.lastname: Berrettini
authors.forename: T N
authors.initials: TN
authors.lastname: Ferraro
authors.forename: L R
authors.initials: LR
authors.lastname: Goldin
authors.forename: S D
authors.initials: SD
authors.lastname: Detera-Wadleigh
authors.forename: H
authors.initials: H
authors.lastname: Choi
authors.forename: D
authors.initials: D
authors.lastname: Muniec
authors.forename: J J
authors.initials: JJ
authors.lastname: Guroff
authors.forename: D M
authors.initials: DM
authors.lastname: Kazuba
authors.forename: J I
authors.initials: JI
authors.lastname: Nurnberger
authors.forename: W T
authors.initials: WT
authors.lastname: Hsieh
authors.forename: M R
authors.initials: MR
authors.lastname: Hoehe
authors.forename: E S
authors.initials: ES
authors.lastname: Gershon
mesh_terms: D001714:Bipolar Disorder / Q000453:epidemiology / Q000235:genetics*; D002887:Chromosomes, Human, Pair 18 / Q000235:genetics; D005260:Female; D008040:Genetic Linkage; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008126:Lod Score; D008297:Male; D008957:Models, Genetic; D010375:Pedigree; D012307:Risk Factors
chemical_list: D005819:Genetic Markers