Schizophrenia in the genetic isolate of Finland

Abstract

We compared the features of schizophrenia in the homogeneous population of Finland (population about 5,000,000) and in an internal isolate in northeastern Finland inhabited in the 1680s by a small group of founders (current population about 18,000) in a register-based epidemiological study. We identified all cases with a diagnosis of schizophrenia in Finland born between 1940-1969 using three national computerized registers and found a total of 267 schizophrenia patients in the internal isolate and 29,124 in Finland. The lifetime prevalence was 2.21% in the internal isolate and 1.21% in Finland, respectively. The age-corrected lifetime risk was 3.2% in the internal isolate and 1.1% in the whole country. The risk of schizophrenia to siblings in the internal isolate was 6.4% (95% confidence interval 0.052, 0.078), 9.1% (95% CI 0.062, 0.130), and 6.8% (95% CI 0.028, 0.135) given 1, 2, or 3 affected siblings, and for all Finland 4.2% (95% CI 0.036, 0.043), 6.4% (95% CI 0.058, 0.071), and 8.7% (95% CI 0.068, 0.107) given 1, 2, or 3, affected siblings, respectively. The mean number of children in schizophrenia families and thus the number of families having at least two affected individuals were clearly higher in the isolate (24.9% vs 9.2%). We did not find any other epidemiological features differing between these two regions. It seems that the family material collected from the internal isolate is a representative subsample from the entire country and hopefully it enables easier identification of at least some predisposing genes for schizophrenia due to its unique population structure.

Replication of linkage on chromosome 7q22 and association of the regional Reelin gene with working memory in schizophrenia families

“…16 The National Public Health Institute of Finland has collected a large family-based schizophrenia study sample. 15,[17][18][19][20][21] In this nationwide series of familial schizophrenia, the major chromosomal regions for linkage are 1q32.2-q42, 2q, 4q31, 5q and 7q22. [22][23][24][25] On 1q42, we have reported a schizophrenia candidate gene DISC1, showing importance especially among males.…”

“…12,13 This is supported by the fact that the lifetime prevalence of schizophrenia in Finland in general is 1.0%, 14 but in an internal isolate in the North-Eastern Finland the agecorrected lifetime morbid risk is as high as 3.2%. 15 Also the higher linkage disequilibrium found between genetic markers make the Finns an excellent study population for complex genetic studies. 16 The National Public Health Institute of Finland has collected a large family-based schizophrenia study sample.…”

Linkage analysis of putative schizophrenia gene candidate regions on chromosomes 3p, 5q, 6p, 8p, 20p and 22q in a population-based sampled Finnish family set

“…8 Patients who had received disability pension or free medication because of schizophrenia were identified from two registers of the Social Insurance Institution, and patients who had been hospitalized for schizophrenia were identified from the National Hospital Discharge Register. All three registers were computerized in 1968; ICD-8 diagnostic criteria and codes were used before 1987, since when psychiatric diagnoses have been coded according to ICD-9 applying DSM-III-R diagnostic criteria.…”

Identification and study of Utah pseudo‐isolate populations—prospects for gene identification

“…It remains controversial whether isolate populations have as much potential for gene identification for complex disorders as they have for rare Mendelian ones [Wright et al, 1999;Shifman and Darvasi, 2001;Heutink and Oostra, 2002;Jorde et al, 2002]. However, there exists ample evidence for successful gene localization and gene isolation for numerous complex disorders in multiple different isolate populations [Hovatta et al, 1997;Cho et al, 2000;Ingvarsson et al, 2001;Gianfrancesco et al, 2003;Venken et al, 2004].…”

“…Genealogic and medical databases can be record linked, allowing identification of highrisk disease pedigrees useful for mapping disease predisposition genes. Population isolates with genealogic and disease registries have been invaluable in the identification of multiple disease genes [e.g., Hovatta et al, 1997;Johnston et al, 2000;Bjornsson et al, 2003;Venken et al, 2004]. However, genetic studies in isolate populations have been limited to those diseases which occur at a high enough frequency in the populations to make such studies informative.…”