TY - JOUR
T1 - The First Genomewide Interaction and Locus-Heterogeneity Linkage Scan in Bipolar Afective Disorder: Strong Evidence of Epistatic Effects between Loci on Chromosomes 2q and 6q
AU - Jamra, R.A.
AU - Fuerst, R.
AU - Kaneva, R.
AU - Diaz, G.O.
AU - Rivas, F.
AU - Mayoral, F.
AU - Gay, E.
AU - Sans, S.
AU - Gonzalez, M.J.
AU - Gil, S.
AU - Cabaleiro, F.
AU - Del Rio, F.
AU - Perez, F.
AU - Haro, J.
AU - Auburger, G.
AU - Milanova, V.
AU - Kostov, C.
AU - Chorbov, V.
AU - Stoyanova, V.
AU - Nikolova-Hill, A.
AU - Onchev, G.
AU - Kremensky, I.
AU - Jablensky, Assen
AU - Schulze, T.G.
AU - Propping, P.
AU - Rietschel, M.
AU - Nothen, M.M.
AU - Cichon, S.
AU - Wienker, T.F.
AU - Schumacher, J.
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 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; and 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.
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 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; and 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.
U2 - 10.1086/521690
DO - 10.1086/521690
M3 - Article
C2 - 17924339
SN - 0002-9297
VL - 81
SP - 974
EP - 986
JO - The American Journal of Human Genetics
JF - The American Journal of Human Genetics
IS - 5
ER -