title: A genome-wide linkage search for bipolar disorder susceptibility loci in a large and complex pedigree from the eastern part of Cuba.
abstract: We present results from a genome-wide scan of a six generation pedigree with 28 affected members with apparently dominant bipolar I disorder from eastern Cuba. Genotypes were obtained using the early access version of the Genechip Mapping 10K Xba array from AFFYMETRIX. Parametric and non-parametric linkage analyses under dominant and recessive models were performed using GENEHUNTER v2.1r5. Two phenotypic models were included in the analyses: bipolar I disorder and recurrent depressive disorder, or bipolar I disorder only. LOD scores were calculated for the entire family combined, and for four subdivisions of the family. For the entire family a suggestive parametric LOD score was obtained under the dominant model and the broader phenotype at 14q11.2-12 (LOD = 2.05). In the same region, a non-parametric LOD score close to genome-wide significance was also obtained, based on the entire family (NPL = 7.31, P-value = 0.07). For two individual branches of the pedigree, genome-wide significance (P < 0.005) was obtained with NPL scores of 8.71 and 12.99, respectively, also in the same region on chromosome 14. Chromosome 5q21.3-22.3 also showed close to genome-wide significant linkage for the complete pedigree (NPL = 7.26, P = 0.07), also supported by significant linkage in one individual branch (NPL = 9.86, P < 0.005). In addition, genome-wide significant nonparametric results (P-values <0.005) were obtained for individual branches at 5p13.1-q12.3, 6p22.3, 8q13.3-21.13, and 10q22.3-23.32. Finally, 2p25.1-25.3, 2p13.3-14, 3p14.2, 6p22.3-24.1, 7p14.1-14.2, 8q12.2-12.3, 10q21.1-21.2, 14q13.1-21.1, 15q15.1-21.2, and 22q12.3-13.32 showed suggestive linkage in the complete family. Most of these potential susceptibility loci overlap with, or are close, to previous linkage findings. The locus on 5q may, however, represent a novel susceptibility locus.
authors.affiliation: National Center of Medical Genetics, Reparto Cubanacán, Playa, Havana, Cuba. beatriz@infomed.sld.cu
authors.forename: B
authors.initials: B
authors.lastname: Marcheco-Teruel
authors.forename: T J
authors.initials: TJ
authors.lastname: Flint
authors.forename: F P
authors.initials: FP
authors.lastname: Wikman
authors.forename: M
authors.initials: M
authors.lastname: Torralbas
authors.forename: L
authors.initials: L
authors.lastname: González
authors.forename: L
authors.initials: L
authors.lastname: Blanco
authors.forename: Q
authors.initials: Q
authors.lastname: Tan
authors.forename: H
authors.initials: H
authors.lastname: Ewald
authors.forename: T
authors.initials: T
authors.lastname: Orntoft
authors.forename: T A
authors.initials: TA
authors.lastname: Kruse
authors.forename: A D
authors.initials: AD
authors.lastname: Børglum
authors.forename: O
authors.initials: O
authors.lastname: Mors
mesh_terms: D001714:Bipolar Disorder / Q000235:genetics*; D002877:Chromosomes, Human / Q000235:genetics*; D003462:Cuba; D005260:Female; D008040:Genetic Linkage; D020022:Genetic Predisposition to Disease; D005820:Genetic Testing; D005838:Genotype; D006801:Humans; D008126:Lod Score; D008297:Male; D008957:Models, Genetic; D020411:Oligonucleotide Array Sequence Analysis; D010375:Pedigree; D010641:Phenotype