title: Genomewide scan and fine-mapping linkage studies in four European samples with bipolar affective disorder suggest a new susceptibility locus on chromosome 1p35-p36 and provides further evidence of loci on chromosome 4q31 and 6q24.
abstract: We present the findings of a large linkage study of bipolar affective disorder (BPAD) that involved genomewide analysis of 52 families (448 genotyped individuals) of Spanish, Romany, and Bulgarian descent and further fine mapping of the 1p34-p36, 4q28-q31, and 6q15-q24 regions. An additional sample of 56 German families (280 individuals) was included for this fine-mapping step. The highest nonparametric linkage scores obtained in the fine mapping were 5.49 for 4q31 and 4.87 for 6q24 in the Romany families and 3.97 for 1p35-p36 in the Spanish sample. MOD-score (LOD scores maximized over genetic model parameters) analysis provided significant evidence of linkage to 4q31 and at least borderline significance for the 1p and 6q regions. On the basis of these results and previous positive research findings, 4q31 and 6q24 should now be considered confirmed BPAD susceptibility loci, and 1p35-p36 is proposed as a new putative locus that requires confirmation in replication studies.
authors.affiliation: Institute of Human Genetics, Life & Brain Center, University of Bonn, D-53105 Bonn, Germany.
authors.forename: Johannes
authors.initials: J
authors.lastname: Schumacher
authors.forename: Radka
authors.initials: R
authors.lastname: Kaneva
authors.forename: Rami Abou
authors.initials: RA
authors.lastname: Jamra
authors.forename: Guillermo Orozco
authors.initials: GO
authors.lastname: Diaz
authors.forename: Stephanie
authors.initials: S
authors.lastname: Ohlraun
authors.forename: Vihra
authors.initials: V
authors.lastname: Milanova
authors.forename: Young-Ae
authors.initials: YA
authors.lastname: Lee
authors.forename: Fabio
authors.initials: F
authors.lastname: Rivas
authors.forename: Fermin
authors.initials: F
authors.lastname: Mayoral
authors.forename: Robert
authors.initials: R
authors.lastname: Fuerst
authors.forename: Antonia
authors.initials: A
authors.lastname: Flaquer
authors.forename: Christine
authors.initials: C
authors.lastname: Windemuth
authors.forename: Eudoxia
authors.initials: E
authors.lastname: Gay
authors.forename: Sebastian
authors.initials: S
authors.lastname: Sanz
authors.forename: Maria José
authors.initials: MJ
authors.lastname: González
authors.forename: Susana
authors.initials: S
authors.lastname: Gil
authors.forename: Francisco
authors.initials: F
authors.lastname: Cabaleiro
authors.forename: Francisco
authors.initials: F
authors.lastname: del Rio
authors.forename: Fermin
authors.initials: F
authors.lastname: Perez
authors.forename: Jesus
authors.initials: J
authors.lastname: Haro
authors.forename: Christian
authors.initials: C
authors.lastname: Kostov
authors.forename: Vesselin
authors.initials: V
authors.lastname: Chorbov
authors.forename: Amelia
authors.initials: A
authors.lastname: Nikolova-Hill
authors.forename: Vessela
authors.initials: V
authors.lastname: Stoyanova
authors.forename: George
authors.initials: G
authors.lastname: Onchev
authors.forename: Ivo
authors.initials: I
authors.lastname: Kremensky
authors.forename: Konstantin
authors.initials: K
authors.lastname: Strauch
authors.forename: Thomas G
authors.initials: TG
authors.lastname: Schulze
authors.forename: Peter
authors.initials: P
authors.lastname: Nürnberg
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Gaebel
authors.forename: Ansgar
authors.initials: A
authors.lastname: Klimke
authors.forename: Georg
authors.initials: G
authors.lastname: Auburger
authors.forename: Thomas F
authors.initials: TF
authors.lastname: Wienker
authors.forename: Luba
authors.initials: L
authors.lastname: Kalaydjieva
authors.forename: Peter
authors.initials: P
authors.lastname: Propping
authors.forename: Sven
authors.initials: S
authors.lastname: Cichon
authors.forename: Assen
authors.initials: A
authors.lastname: Jablensky
authors.forename: Marcella
authors.initials: M
authors.lastname: Rietschel
authors.forename: Markus M
authors.initials: MM
authors.lastname: Nöthen
mesh_terms: D001714:Bipolar Disorder / Q000235:genetics; D002031:Bulgaria / Q000208:ethnology; D002878:Chromosomes, Human, Pair 1 / Q000235:genetics*; D002894:Chromosomes, Human, Pair 4 / Q000235:genetics*; D002896:Chromosomes, Human, Pair 6 / Q000235:genetics*; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease; D015894:Genome, Human; D005858:Germany / Q000208:ethnology; D006801:Humans; D008126:Lod Score; D020161:Physical Chromosome Mapping; D006178:Romani People / Q000208:ethnology; D013030:Spain / Q000208:ethnology; D044465:White People / Q000208:ethnology / Q000706:statistics & numerical data
chemical_list: D005819:Genetic Markers