TY - JOUR
T1 - A linkage study of bipolar illness
AU - Berrettini, Wade H.
AU - Ferraro, Thomas N.
AU - Goldin, Lynn R.
AU - Detera-Wadleigh, Sevilla D.
AU - Choi, Henry
AU - Muniec, David
AU - Guroff, Juliet J.
AU - Kazuba, Diane M.
AU - Nurnberger, John I.
AU - Hsieh, Wang Ting
AU - Hoehe, Margret R.
AU - Gershon, Elliot S.
N1 - Funding Information:
Gerkin,DavidCallen,andJeanWeissenbachforprovid¬ ingunpublishedprimersequencesfornumerous microsat¬ ellites.Wethankthefollowingpersonsforprovidingprobes: IngridCaras(DAF),SandraGendler(MUC1),Nicholas Dracopoli(D1S9,D1S13,D1S14,D1S15,andFGR), M. Goossens (PBGD),S.K.Karathanasis (AP0A1),CliveDick- sonandG.Peters(INT-2),SpurrN.K.(STMYandCDC2), E. Dietzsch (D11S29), Brian KobilkaandRobert Lefko-witz(alpha2CÍO),andV.Ramesh(HOAT-1),ProfC.T.H.C.M. Buys(D13S11,D13S12, D13S22), Dryja(RB), W. Cavenee(D13S39andD13S41),A.E.Bale(D13S31, D13S32,andD13S35),D.Barker(D17S58,D17S40, Dl7S57,andDI7S73),M.V.Chao(NGFR),K.K.Kidd (TK1),JohnArmour(D18S32,D18S31,D13S70,D8S162,and D12S41,D12S42,D14S22,D14S44,D15S86, D16S309),GillesVergnaud(D13S107),Jean-Louis Mandel (D18S3),UtaFranche(SSAVl),Jean-Pierre Julien (NEFL), EliotSpindel (GRP), Stanley Prusiner (MBP), IvanBalazs(D18S27andD14S1),PerrinWhite(CYP11B1), and Carlo Croce (MYC). We thank themanyinvestiga¬ tors who made theirprobesavailabletousthroughthe AmericanTypeCultureCollection.D12S65wasprovided byWetheJapanesethetechnicalassistanceCancerResearchResourcesBank. gratefullyacknowledge ofNinaHarris,ChrisBailas,AmyWagner,DavidHeydt, JoanBarrick, TeresaCollela,MiaNorlin,andCharlesCap- pellari.WethankJessicaVasermanforherassistancein theexclusionmappinganalysis,JaniceEgeland,PhD,for making the Old Order Amish pedigree samples available through forResearch, wheremanyofthesecelllinesarestored.Thesiblingpair resultsofthisarticlewereobtainedusingtheprogrampack¬ ageSAGE([1992]StatisticalAnalysisforGeneticEpi¬ demiology, Release 2.1. Computer program package avail¬ from Department ofBiometry Genetics, LouisianaStateUniversityMedicalCenter,NewOr¬ leans), which is supported by US Public Health Service ResourceGrant 1 P41 RR03655from theDivisionofRe¬ searchResources.WethankM.ElizabethMaxwell,MSW, Anne L. Smith, MSW,JulietJ. Guroff MSW, Diane M. Kazubajoel Hamovit, MSW, Susan Simmons-Ailing, MSN, CarolynYork,andMarvinBrown,MD,forclinical assis¬ tanceinpedigreecollection.Wethankthefamilieswho participated,IIIandtheNationalAlliancefortheMentally forencouragingfamilyparticipation. Reprints:WadeH.Berrettini,MD,PhD,ThomasJef¬ ferson University, Department ofPsychiatry and Human Behavior,1025WalnutSt,312College,Philadelphia,PA 19107(e-mail:[email protected]).
Funding Information:
This study was supported by an Established Investi¬ gatorAward(DrBerrettini)andaYoungInvestigatorAward (Dr Ferraro) fromand the National AllianceforandResearch on Schizophrenia Depression, Chicago, III, by grant MH49181fromtheNationalInstituteofMentalHealth, dation MdAdvanced(DrBerrettini),EducationandintheaSciences,totheBethesda,Foun¬ byAnitaforKaskel Roe.
PY - 1997
Y1 - 1997
N2 - 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 compel ling 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.
AB - 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 compel ling 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.
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U2 - 10.1001/archpsyc.1997.01830130031006
DO - 10.1001/archpsyc.1997.01830130031006
M3 - Article
C2 - 9006397
AN - SCOPUS:15144347946
SN - 0003-990X
VL - 54
SP - 27
EP - 35
JO - Archives of General Psychiatry
JF - Archives of General Psychiatry
IS - 1
ER -