title: The first genomewide interaction and locus-heterogeneity linkage scan in bipolar affective disorder: strong evidence of epistatic effects between loci on chromosomes 2q and 6q.
abstract: We present the first genomewide interaction and locus-heterogeneity linkage scan in bipolar affective disorder (BPAD), using a large linkage data set (52 families of European descent; 448 participants and 259 affected individuals). Our results provide the strongest interaction evidence between BPAD genes on chromosomes 2q22-q24 and 6q23-q24, which was observed symmetrically in both directions (nonparametric LOD [NPL] scores of 7.55 on 2q and 7.63 on 6q; P<.0001 and P=.0001, respectively, after a genomewide permutation procedure). The second-best BPAD interaction evidence was observed between chromosomes 2q22-q24 and 15q26. Here, we also observed a symmetrical interaction (NPL scores of 6.26 on 2q and 4.59 on 15q; P=.0057 and .0022, respectively). We covered the implicated regions by genotyping additional marker sets and performed a detailed interaction linkage analysis, which narrowed the susceptibility intervals. Although the heterogeneity analysis produced less impressive results (highest NPL score of 3.32) and a less consistent picture, we achieved evidence of locus heterogeneity at chromosomes 2q, 6p, 11p, 13q, and 22q, which was supported by adjacent markers within each region and by previously reported BPAD linkage findings. Our results provide systematic insights in the framework of BPAD epistasis and locus heterogeneity, which should facilitate gene identification by the use of more-comprehensive cloning strategies.
authors.affiliation: Institute of Human Genetics, University of Bonn, Bonn, Germany.
authors.forename: Rami
authors.initials: R
authors.lastname: Abou Jamra
authors.forename: Robert
authors.initials: R
authors.lastname: Fuerst
authors.forename: Radka
authors.initials: R
authors.lastname: Kaneva
authors.forename: Guillermo
authors.initials: G
authors.lastname: Orozco Diaz
authors.forename: Fabio
authors.initials: F
authors.lastname: Rivas
authors.forename: Fermin
authors.initials: F
authors.lastname: Mayoral
authors.forename: Eudoxia
authors.initials: E
authors.lastname: Gay
authors.forename: Sebastian
authors.initials: S
authors.lastname: Sans
authors.forename: Maria Jose
authors.initials: MJ
authors.lastname: Gonzalez
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: Georg
authors.initials: G
authors.lastname: Auburger
authors.forename: Vihra
authors.initials: V
authors.lastname: Milanova
authors.forename: Christian
authors.initials: C
authors.lastname: Kostov
authors.forename: Vesselin
authors.initials: V
authors.lastname: Chorbov
authors.forename: Vessela
authors.initials: V
authors.lastname: Stoyanova
authors.forename: Amelia
authors.initials: A
authors.lastname: Nikolova-Hill
authors.forename: George
authors.initials: G
authors.lastname: Onchev
authors.forename: Ivo
authors.initials: I
authors.lastname: Kremensky
authors.forename: Assen
authors.initials: A
authors.lastname: Jablensky
authors.forename: Thomas G
authors.initials: TG
authors.lastname: Schulze
authors.forename: Peter
authors.initials: P
authors.lastname: Propping
authors.forename: Marcella
authors.initials: M
authors.lastname: Rietschel
authors.forename: Markus M
authors.initials: MM
authors.lastname: Nothen
authors.forename: Sven
authors.initials: S
authors.lastname: Cichon
authors.forename: Thomas F
authors.initials: TF
authors.lastname: Wienker
authors.forename: Johannes
authors.initials: J
authors.lastname: Schumacher
mesh_terms: D001714:Bipolar Disorder / Q000235:genetics*; D002874:Chromosome Mapping; D002884:Chromosomes, Human, Pair 15 / Q000235:genetics; D002889:Chromosomes, Human, Pair 2 / Q000235:genetics*; D002896:Chromosomes, Human, Pair 6 / Q000235:genetics*; D004843:Epistasis, Genetic; D018740:Genetic Heterogeneity; D008040:Genetic Linkage; D005819:Genetic Markers; D005820:Genetic Testing; D015894:Genome, Human / Q000235:genetics*; D006801:Humans
chemical_list: D005819:Genetic Markers