TY - JOUR
T1 - The first genomewide interaction and locus-heterogeneity linkage scan in bipolar affective disorder
T2 - Strong evidence of epistatic effects between loci on chromosomes 2q and 6q
AU - Jamra, Rami Abou
AU - Fuerst, Robert
AU - Kaneva, Radka
AU - Diaz, Guillermo Orozco
AU - Rivas, Fabio
AU - Mayoral, Fermin
AU - Gay, Eudoxia
AU - Sans, Sebastian
AU - González, Maria Jose
AU - Gil, Susana
AU - Cabaleiro, Francisco
AU - Del Rio, Francisco
AU - Perez, Fermin
AU - Haro, Jesus
AU - Auburger, Georg
AU - Milanova, Vihra
AU - Kostov, Christian
AU - Chorbov, Vesselin
AU - Stoyanova, Vessela
AU - Nikolova-Hill, Amelia
AU - Onchev, George
AU - Kremensky, Ivo
AU - Jablensky, Assen
AU - Schulze, Thomas G.
AU - Propping, Peter
AU - Rietschel, Marcella
AU - Nöthen, Markus M.
AU - Cichon, Sven
AU - Wienker, Thomas F.
AU - Schumacher, Johannes
PY - 2007
Y1 - 2007
N2 - 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 , respectively, after a genomewide permutation procedure). The second-best BPAD interaction evidence P = .0001 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; and .0022, respectively). We covered the implicated regions by genotyping P = .0057 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.
AB - 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 , respectively, after a genomewide permutation procedure). The second-best BPAD interaction evidence P = .0001 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; and .0022, respectively). We covered the implicated regions by genotyping P = .0057 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.
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U2 - 10.1086/521690
DO - 10.1086/521690
M3 - Article
C2 - 17924339
AN - SCOPUS:35348832886
SN - 0002-9297
VL - 81
SP - 974
EP - 986
JO - American Journal of Human Genetics
JF - American Journal of Human Genetics
IS - 5
ER -