title: Initial genome scan of the NIMH genetics initiative bipolar pedigrees: chromosomes 4, 7, 9, 18, 19, 20, and 21q.
abstract: An initial genome scan was performed on 540 individuals from 97 families segregating bipolar disorder, collected through the National Institutes of Mental Health Genetics Initiative. We report here affected-sib-pair (ASP) data on 126 marker loci (approximately 68,000 genotypes) mapping to chromosomes 4, 7, 9, 18, 19, 20, and 21q, under three affection status models. Modest increases in identical-by-descent (IBD) allele sharing were found at the following loci: D4S2397 and D4S391 (P < 0.05) on 4p, D4S1647 (P < 0.05) on 4q, D7S1802 and D7S1869 (low P = 0.01) on 7p, D9S302 (P = 0.004) on 9q, and D20S604 on 20p and D20S173 on 20q (P < 0.05). In addition, five markers on 7q displayed increased IBD sharing (P = 0.046-0.002). Additional ASP analyses on chromosomes 18 and 21q marker data were performed using disease phenotype models defined previously. On chromosome 18, only D18S40 on 18p and D18S70 on 18q yielded a slight elevation in allele sharing (P = 0.02), implying that the reported linkages in these regions were not confirmed. On chromosome 21q, a cluster of markers within an approximately 9 cM interval: D21S1254, D21S65, D21S1440, and D21S1255 exhibited excess allele sharing (P = 0.041-0.008). Multilocus data on overlapping marker quartets, from D21S1265 to D21S1255, which were consistent with increased IBD sharing (P < 0.01, with a low of 0.0009), overlapped a broad interval of excess allele sharing reported previously, increasing support for a susceptibility locus for bipolar disorder on 21q.
authors.affiliation: Clinical Neurogenetics Branch, National Institute of Mental Health, National Institutes of Health, Bethesda, Maryland 20892, USA.
authors.forename: S D
authors.initials: SD
authors.lastname: Detera-Wadleigh
authors.forename: J A
authors.initials: JA
authors.lastname: Badner
authors.forename: T
authors.initials: T
authors.lastname: Yoshikawa
authors.forename: A R
authors.initials: AR
authors.lastname: Sanders
authors.forename: L R
authors.initials: LR
authors.lastname: Goldin
authors.forename: G
authors.initials: G
authors.lastname: Turner
authors.forename: D Y
authors.initials: DY
authors.lastname: Rollins
authors.forename: T
authors.initials: T
authors.lastname: Moses
authors.forename: J J
authors.initials: JJ
authors.lastname: Guroff
authors.forename: D
authors.initials: D
authors.lastname: Kazuba
authors.forename: M E
authors.initials: ME
authors.lastname: Maxwell
authors.forename: H J
authors.initials: HJ
authors.lastname: Edenberg
authors.forename: T
authors.initials: T
authors.lastname: Foroud
authors.forename: D
authors.initials: D
authors.lastname: Lahiri
authors.forename: J I
authors.initials: JI
authors.lastname: Nurnberger
authors.forename: O C
authors.initials: OC
authors.lastname: Stine
authors.forename: F
authors.initials: F
authors.lastname: McMahon
authors.forename: D A
authors.initials: DA
authors.lastname: Meyers
authors.forename: D
authors.initials: D
authors.lastname: MacKinnon
authors.forename: S
authors.initials: S
authors.lastname: Simpson
authors.forename: M
authors.initials: M
authors.lastname: McInnis
authors.forename: J R
authors.initials: JR
authors.lastname: DePaulo
authors.forename: J
authors.initials: J
authors.lastname: Rice
authors.forename: A
authors.initials: A
authors.lastname: Goate
authors.forename: E S
authors.initials: ES
authors.lastname: Gershon
mesh_terms: D000483:Alleles; D001714:Bipolar Disorder / Q000235:genetics*; D002874:Chromosome Mapping; D002887:Chromosomes, Human, Pair 18; D002888:Chromosomes, Human, Pair 19; D002890:Chromosomes, Human, Pair 20; D002891:Chromosomes, Human, Pair 21; D002894:Chromosomes, Human, Pair 4; D002897:Chromosomes, Human, Pair 7; D002899:Chromosomes, Human, Pair 9; D005260:Female; D008040:Genetic Linkage; D005819:Genetic Markers; D015894:Genome, Human; D005838:Genotype; D006801:Humans; D008297:Male; D009315:National Institute of Mental Health (U.S.); D009679:Nuclear Family; D010375:Pedigree; D014481:United States
chemical_list: D005819:Genetic Markers