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A linkage study of bipolar illness

Item Type:Article
Title:A linkage study of bipolar illness
Creators Name:Berrettini, W.H., Ferraro, T.N., Goldin, L.R., Detera-Wadleigh, S., Choi, H., Muniec, D., Guroff, J.J., Kazuba, D.M., Nurnberger, J.I., Hsieh, W.T., Hoehe, M.R. and Gershon, E.S.
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.
Keywords:Bipolar Disorder, Human Chromosomes Pair 18, Genetic Markers, Genetic Predisposition to Disease, Genotype, Linkage (Genetics), Lod Score, Genetic Models, Pedigree, Risk Factors
Source:Archives of General Psychiatry
ISSN:0003-990X
Publisher:American Medical Association
Volume:54
Number:1
Page Range:27-35
Date:January 1997
Official Publication:http://archpsyc.ama-assn.org/cgi/content/abstract/54/1/27
PubMed:View item in PubMed

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