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Human Molecular Genetics, 2003, Vol. 12, No. 15 1907-1915
DOI: 10.1093/hmg/ddg199
© 2003 Oxford University Press

Evidence of susceptibility loci on 4q32 and 16p12 for bipolar disorder

Jenny M. Ekholm1,3, Tuula Kieseppä2, Tero Hiekkalinna1,3, Timo Partonen2, Tiina Paunio1,4, Markus Perola1,3, Jesper Ekelund1,2, Jouko Lönnqvist2, Petra Pekkarinen-Ijäs1,2,5 and Leena Peltonen1,3,*

1Department of Molecular Medicine and 2Department of Mental Health and Alcohol Research, National Public Health Institute, 00251 Helsinki, Finland, 3Department of Human Genetics, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, USA, 4Department of Psychiatry, University of Helsinki, Helsinki, Finland and 5Department of Neurology, Helsinki University Central Hospital, Helsinki, Finland

Received March 26, 2003; Accepted June 3, 2003

We performed a genome-wide scan for susceptibility loci in bipolar disorder in a study sample colleted from the isolated Finnish population, consisting of 41 families with at least two affected siblings. We identified one distinct locus on 16p12 providing significant evidence for linkage in two-point analysis (Zmax=3.4). Furthermore, three loci with a two-point LOD score >2.0 were observed with markers on 4q32, 12q23 and Xq25, the latter locus having been earlier identified in one extended Finnish pedigree. In the second stage we fine mapped these chromosomal regions and also genotyped additional family members. In the fine mapping stage, 4q32 provided significant evidence of linkage for the three-point analyses (Zmax=3.6) and 16p12 produced a three-point LOD score of 2.7. Since the identified chromosomal regions replicate earlier linkage findings in either bipolar disorder or other mental disorders, they should be considered good targets for further genetic analyses.

* To whom correspondence should be addressed. Tel: +358 947448393; Fax: +358 947448480; Email: leena.peltonen{at}ktl.fi


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