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.
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.
Abou Jamra
Rami
R
Institute of Human Genetics, University of Bonn, Bonn, Germany.
Fuerst
Robert
R
Kaneva
Radka
R
Orozco Diaz
Guillermo
G
Rivas
Fabio
F
Mayoral
Fermin
F
Gay
Eudoxia
E
Sans
Sebastian
S
Gonzalez
Maria Jose
MJ
Gil
Susana
S
Cabaleiro
Francisco
F
Del Rio
Francisco
F
Perez
Fermin
F
Haro
Jesus
J
Auburger
Georg
G
Milanova
Vihra
V
Kostov
Christian
C
Chorbov
Vesselin
V
Stoyanova
Vessela
V
Nikolova-Hill
Amelia
A
Onchev
George
G
Kremensky
Ivo
I
Jablensky
Assen
A
Schulze
Thomas G
TG
Propping
Peter
P
Rietschel
Marcella
M
Nothen
Markus M
MM
Cichon
Sven
S
Wienker
Thomas F
TF
Schumacher
Johannes
J
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
D005819:Genetic Markers