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Human Molecular Genetics, 2000, Vol. 9, No. 7 1049-1057
© 2000 Oxford University Press

Genome-wide scan for schizophrenia in the Finnish population: evidence for a locus on chromosome 7q22

Jesper Ekelund1,2, Dirk Lichtermann1,2,+, Iiris Hovatta1,2, Pekka Ellonen1, Jaana Suvisaari2, Joseph D. Terwilliger3, Hannu Juvonen2, Teppo Varilo1, Ritva Arajärvi2, Marja-Liisa Kokko-Sahin2, Jouko Lönnqvist2 and Leena Peltonen1,§

1Department of Human Molecular Genetics and 2Department of Mental Health and Alcohol Research, National Public Health Institute, Helsinki, Finland and 3Department of Psychiatry and Columbia Genome Center, Columbia University, New York, NY, USA

We report the results of a four-stage genome-wide scan in a schizophrenia study sample consisting of 134 affected sib-pairs collected in Finland. In stage I we genotyped 370 markers from the Weber 6 screening set (N = 52 affected sib-pairs); in stage II we followed up 40 markers by typing first-degree relatives of the sib-pairs; in stage III we genotyped 15 markers in 134 families; and in stage IV we genotyped a denser marker map in the two most promising regions, one on chromosome 1 and another on chromosome 7, in all families. Diagnoses were based on three nationwide health care registers and consensus diagnosis based on review of all medical records. The most significant finding was a two-point lod score of 3.18 with marker D7S486 using a dominant model and treating all individuals with either schizophrenia, schizoaffective disorder or other schizophrenia spectrum disorder as affected. Multipoint analysis with MAPMAKER/SIBS resulted in a MLS of 3.53 between markers D7S501 and D7S523 using the broadest diagnostic model, including major depressive disorder and bipolar type I as affecteds in addition to the aforementioned phenotypes. These results were obtained by including in the analyses only individuals from the late settlement region of Finland settled in the 16th century. Additionally, some support was obtained for linkage to chromosome 1, in a region previously identified in a genome-wide scan of a study sample from a sub-isolate of Finland. Our data demonstrate the importance of genealogical information for studies aiming at identification of predisposing loci in complex diseases.

+ Present address: Department of Psychiatry, University of Bonn, Bonn, Germany

§ To whom correspondence should be addressed at present address: Department of Human Genetics, UCLA School of Medicine, Gonda Center, 695 Charles E. Young Drive South, Box 708822, Los Angeles, CA 90095-7088, USA. Tel: +1 310 794 5631; Fax: +1 310 794 5446; Email: lpeltonen@mednet.ucla.edu


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