title: Initial genome screen for bipolar disorder in the NIMH genetics initiative pedigrees: chromosomes 2, 11, 13, 14, and X.
abstract: We report on an initial genome screen of 540 individuals from 97 families collected as part of the NIMH Genetics Initiative Bipolar Group. Among the individuals studied, 232 were diagnosed with bipolar (BP) I, 72 with BPII, 88 with major depressive disorder-recurrent type (UPR), and 32 with schizoaffective disorder, bipolar type (SA/BP). A total of 53 markers on chromosomes 2, 11, 13, 14, and X (average spacing: 11.5 cM) were studied at Johns Hopkins University. Tests for linkage were performed using nonparametric affected sib-pair and whole pedigree methods with three definitions of affected status. Three regions of interest were identified (13q14-32, Xp22, and Xq26-28). On chromosomes 2, 11, and 14, a disease locus with relative risk lambda(i) = 1.5 could be excluded in <10% of the genetic distance studied, while a locus conferring lambda(i) = 3 or greater could be excluded across at least 96%. The autosomal region that could not be excluded even with lambda(i) = 5 was near 13q14-32. In this region, two-point affected sib-pair analyses revealed a pair of consecutive loci with excess sharing (P < 0.05) and a multipoint affected sib-pair LOD score of 1.12. On the X chromosome, nonparametric multipoint affected sib-pair analyses revealed peak total LOD scores of 0.94 on Xp22 and 1.34 on Xq26-28. A locus linked to the markers in Xp22 would have lambda(i) = 3.6 in affected brother-brother pairs, while a locus linked to the markers in Xq26-28 would have lambda(i) > 1.9 in affected sister-sister pairs. The results on 13q14-32, Xp22, and Xq26-28 suggest areas of interest for further studies.
authors.affiliation: Department of Psychiatry, Johns Hopkins University School of Medicine, Baltimore, Maryland 21287-7381, USA.
authors.forename: O C
authors.initials: OC
authors.lastname: Stine
authors.forename: F J
authors.initials: FJ
authors.lastname: McMahon
authors.forename: L
authors.initials: L
authors.lastname: Chen
authors.forename: J
authors.initials: J
authors.lastname: Xu
authors.forename: D A
authors.initials: DA
authors.lastname: Meyers
authors.forename: D F
authors.initials: DF
authors.lastname: MacKinnon
authors.forename: S
authors.initials: S
authors.lastname: Simpson
authors.forename: M G
authors.initials: MG
authors.lastname: McInnis
authors.forename: J P
authors.initials: JP
authors.lastname: Rice
authors.forename: A
authors.initials: A
authors.lastname: Goate
authors.forename: T
authors.initials: T
authors.lastname: Reich
authors.forename: H J
authors.initials: HJ
authors.lastname: Edenberg
authors.forename: T
authors.initials: T
authors.lastname: Foroud
authors.forename: J I
authors.initials: JI
authors.lastname: Nurnberger
authors.forename: S D
authors.initials: SD
authors.lastname: Detera-Wadleigh
authors.forename: L R
authors.initials: LR
authors.lastname: Goldin
authors.forename: J
authors.initials: J
authors.lastname: Guroff
authors.forename: E S
authors.initials: ES
authors.lastname: Gershon
authors.forename: M C
authors.initials: MC
authors.lastname: Blehar
authors.forename: J R
authors.initials: JR
authors.lastname: DePaulo
mesh_terms: D001714:Bipolar Disorder / Q000235:genetics*; D002880:Chromosomes, Human, Pair 11; D002882:Chromosomes, Human, Pair 13; D002883:Chromosomes, Human, Pair 14; D002889:Chromosomes, Human, Pair 2; D005260:Female; D008040:Genetic Linkage; D005819:Genetic Markers; D015894:Genome, Human; D006801:Humans; D008126:Lod Score; D008297:Male; D009315:National Institute of Mental Health (U.S.); D009679:Nuclear Family; D010375:Pedigree; D018709:Statistics, Nonparametric; D014481:United States; D014960:X Chromosome
chemical_list: D005819:Genetic Markers