A genomewide screen for schizophrenia genes in an isolated Finnish subpopulation, suggesting multiple susceptibility loci.

Abstract

Schizophrenia is a severe mental disorder affecting approximately 1% of the world's population. Here, we report the results from a three-stage genomewide screen performed in a study sample from an internal isolate of Finland. An effort was made to identify genes predisposing for schizophrenia that are potentially enriched in this isolate, which has an exceptionally high lifetime risk for this trait. Ancestors of the local families with schizophrenia were traced back to the foundation of the population in the 17th century. This genealogical information was used as the basis for the study strategy, which involved screening for alleles shared among affected individuals originating from common ancestors. We found four chromosomal regions with markers revealing pairwise LOD scores>1.0: 1q32.2-q41 (Z(max)=3.82, dominant affecteds-only model), 4q31 (Z(max)=2. 74, dominant 90%-penetrance model), 9q21 (Z(max)=1.95, dominant 90%-penetrance model), and Xp11.4-p11.3 (Z(max)=2.01, recessive 90%-penetrance model). This finding suggests that there are several putative loci predisposing to schizophrenia, even in this isolate.