title: Chromosome 10q harbors a susceptibility locus for bipolar disorder in Ashkenazi Jewish families.
abstract: We report the results of a 10 cM density genome-wide scan and further fine mapping of three chromosomal candidate regions in 10 Belgian multigenerational families with bipolar (BP) disorder. This two-stage approach revealed significant evidence for linkage on chromosome 10q21.3-10q22.3, showing a maximum multipoint parametric heterogeneity logarithm of odds (HLOD) score of 3.28 and a nonparametric linkage (NPL) score of 4.00. Most of the chromosome 10q evidence was derived from a single, large Ashkenazi Jewish pedigree. Haplotype analysis in this pedigree shows that the patients share a 14-marker haplotype, defining a chromosomal candidate region of 19.2 cM. This region was reported previously as a candidate region for BP disorder in several independent linkage analysis studies and in one large meta-analysis. It was also implicated in a linkage study on schizophrenia (SZ) in Ashkenazi Jewish families. Additionally, we found suggestive evidence for linkage on chromosome 19q13.2-13.4 (HLOD 2.01, NPL 1.09) and chromosome 7q21-q22 (HLOD 1.45, NPL 2.28). Together, these observations suggest that a gene located on chromosome 10q21.3-10q22.3 is underlying the susceptibility both for SZ and for BP disorder in at least the Ashkenazi Jewish population.
authors.affiliation: Department of Molecular Genetics, Flanders Institute for Biotechnology VIB, Antwerpen, Belgium.
authors.forename: T
authors.initials: T
authors.lastname: Venken
authors.forename: M
authors.initials: M
authors.lastname: Alaerts
authors.forename: D
authors.initials: D
authors.lastname: Souery
authors.forename: D
authors.initials: D
authors.lastname: Goossens
authors.forename: S
authors.initials: S
authors.lastname: Sluijs
authors.forename: R
authors.initials: R
authors.lastname: Navon
authors.forename: C
authors.initials: C
authors.lastname: Van Broeckhoven
authors.forename: J
authors.initials: J
authors.lastname: Mendlewicz
authors.forename: J
authors.initials: J
authors.lastname: Del-Favero
authors.forename: S
authors.initials: S
authors.lastname: Claes
mesh_terms: D000328:Adult; D001714:Bipolar Disorder / Q000235:genetics*; D002874:Chromosome Mapping / Q000379:methods; D002879:Chromosomes, Human, Pair 10; D005192:Family Health; D005260:Female; D008040:Genetic Linkage; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D007585:Jews; D008126:Lod Score; D008297:Male; D016017:Odds Ratio