Genome-wide scan for schizophrenia in the Finnish population: evidence for a locus on chromosome 7q22.
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.
Ekelund
J
J
Department of Human Molecular Genetics, National Public Health Institute, Helsinki, Finland.
Lichtermann
D
D
Hovatta
I
I
Ellonen
P
P
Suvisaari
J
J
Terwilliger
J D
JD
Juvonen
H
H
Varilo
T
T
Arajärvi
R
R
Kokko-Sahin
M L
ML
Lönnqvist
J
J
Peltonen
L
L
D000328:Adult; D002874:Chromosome Mapping; D002878:Chromosomes, Human, Pair 1; D002897:Chromosomes, Human, Pair 7; D005192:Family Health; D005260:Female; D005387:Finland; D008040:Genetic Linkage; D005819:Genetic Markers; D005838:Genotype; D006801:Humans; D016013:Likelihood Functions; D008126:Lod Score; D008297:Male; D008875:Middle Aged; D011159:Population Surveillance; D012559:Schizophrenia / Q000235:genetics*
D005819:Genetic Markers