1. ¹Department of Molecular Genetics, Flanders Institute for Biotechnology VIB, Antwerpen, Belgium
2. ²University of Antwerp, Antwerpen, Belgium
3. ³Department of Psychiatry, Erasme Hospital, University of Brussels, Brussels, Belgium
4. ⁴Department of Human Molecular Genetics and Biochemistry, Sackler School of Medicine, University of Tel Aviv, Tel Aviv, Israel

Correspondence: Professor Dr J Del-Favero, Applied Molecular Genomics Group, Department of Molecular Genetics, VIB, University of Antwerp, Campus CDE, Parking P4, Building V, Room 1.14, Universiteitsplein 1, BE-2610 Antwerpen, Belgium. E-mail: jurgen.delfavero@ua.ac.be

⁵Current address: Department of Psychiatry, University Hospital Gasthuisberg, Leuven, Belgium.

Received 10 January 2007; Revised 19 April 2007; Accepted 7 May 2007; Published online 19 June 2007.

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.