Chromosome 10q harbors a susceptibility locus for bipolar disorder in Ashkenazi Jewish families
Venken, T × Alaerts, M Souery, D Goossens, D Sluijs, S Navon, R Van Broeckhoven, C Mendlewicz, J Del-Favero, J Claes, Stephan #
Molecular Psychiatry vol:13 issue:4 pages:442-450
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.Molecular Psychiatry advance online publication, 19 June 2007; doi:10.1038/sj.mp.4002039.