title: Genomewide linkage analyses of bipolar disorder: a new sample of 250 pedigrees from the National Institute of Mental Health Genetics Initiative.
abstract: We conducted genomewide linkage analyses on 1,152 individuals from 250 families segregating for bipolar disorder and related affective illnesses. These pedigrees were ascertained at 10 sites in the United States, through a proband with bipolar I affective disorder and a sibling with bipolar I or schizoaffective disorder, bipolar type. Uniform methods of ascertainment and assessment were used at all sites. A 9-cM screen was performed by use of 391 markers, with an average heterozygosity of 0.76. Multipoint, nonparametric linkage analyses were conducted in affected relative pairs. Additionally, simulation analyses were performed to determine genomewide significance levels for this study. Three hierarchical models of affection were analyzed. Significant evidence for linkage (genomewide P<.05) was found on chromosome 17q, with a peak maximum LOD score of 3.63, at the marker D17S928, and on chromosome 6q, with a peak maximum LOD score of 3.61, near the marker D6S1021. These loci met both standard and simulation-based criteria for genomewide significance. Suggestive evidence of linkage was observed in three other regions (genomewide P<.10), on chromosomes 2p, 3q, and 8q. This study, which is based on the largest linkage sample for bipolar disorder analyzed to date, indicates that several genes contribute to bipolar disorder.
authors.affiliation: Institute of Psychiatric Research, Indiana University School of Medicine, 791 Union Drive, Indianapolis, IN 46202-4887, USA.
authors.forename: Danielle M
authors.initials: DM
authors.lastname: Dick
authors.forename: Tatiana
authors.initials: T
authors.lastname: Foroud
authors.forename: Leah
authors.initials: L
authors.lastname: Flury
authors.forename: Elizabeth S
authors.initials: ES
authors.lastname: Bowman
authors.forename: Marvin J
authors.initials: MJ
authors.lastname: Miller
authors.forename: N Leela
authors.initials: NL
authors.lastname: Rau
authors.forename: P Ryan
authors.initials: PR
authors.lastname: Moe
authors.forename: Nalini
authors.initials: N
authors.lastname: Samavedy
authors.forename: Rif
authors.initials: R
authors.lastname: El-Mallakh
authors.forename: Husseini
authors.initials: H
authors.lastname: Manji
authors.forename: Debra A
authors.initials: DA
authors.lastname: Glitz
authors.forename: Eric T
authors.initials: ET
authors.lastname: Meyer
authors.forename: Carrie
authors.initials: C
authors.lastname: Smiley
authors.forename: Rhoda
authors.initials: R
authors.lastname: Hahn
authors.forename: Clifford
authors.initials: C
authors.lastname: Widmark
authors.forename: Rebecca
authors.initials: R
authors.lastname: McKinney
authors.forename: Laura
authors.initials: L
authors.lastname: Sutton
authors.forename: Christos
authors.initials: C
authors.lastname: Ballas
authors.forename: Dorothy
authors.initials: D
authors.lastname: Grice
authors.forename: Wade
authors.initials: W
authors.lastname: Berrettini
authors.forename: William
authors.initials: W
authors.lastname: Byerley
authors.forename: William
authors.initials: W
authors.lastname: Coryell
authors.forename: Raymond
authors.initials: R
authors.lastname: DePaulo
authors.forename: Dean F
authors.initials: DF
authors.lastname: MacKinnon
authors.forename: Elliot S
authors.initials: ES
authors.lastname: Gershon
authors.forename: John R
authors.initials: JR
authors.lastname: Kelsoe
authors.forename: Francis J
authors.initials: FJ
authors.lastname: McMahon
authors.forename: Melvin
authors.initials: M
authors.lastname: McInnis
authors.forename: Dennis L
authors.initials: DL
authors.lastname: Murphy
authors.forename: Theodore
authors.initials: T
authors.lastname: Reich
authors.forename: William
authors.initials: W
authors.lastname: Scheftner
authors.forename: John I
authors.initials: JI
authors.lastname: Nurnberger
mesh_terms: D001714:Bipolar Disorder / Q000235:genetics*; D005260:Female; D008040:Genetic Linkage; D005824:Genetics, Behavioral; D015894:Genome, Human; D006801:Humans; D008297:Male; D009316:National Institutes of Health (U.S.); D010375:Pedigree; D014481:United States