The Genetic Epidemiology of Schizophrenia in a Finnish Twin Cohort

TLDR

Schizophrenia heritability estimates are controversial because prior studies relied solely on index twin pairs. The authors aimed to quantify the genetic and environmental contributions to schizophrenia liability using structural equation modeling in a population-based Finnish twin cohort. They screened 3,445 monozygotic and 5,878 same-sex dizygotic twins born 1940–1957 for nonorganic psychotic disorders recorded in inpatient, outpatient, or disability pension data. The lifetime prevalence of schizophrenia was 2.0% (2.2% in men, 1.8% in women), and additive genetic factors accounted for 83% of liability variance while unique environmental factors contributed 17%, with no sex‑specific genetic effects and heritability estimates consistent with recent studies.

Abstract

<h3>Background</h3> The magnitude of heritability of schizophrenia remains controversial, due in part to limitations of estimates derived from index twin pairs exclusively. We applied structural equation modeling in a total population of twins to determine the significance and magnitudes of the genetic and environmental contributions to schizophrenia. <h3>Methods</h3> All monozygotic (1180 male and 1315 female pairs) and same-sex dizygotic (2765 male and 2613 female pairs) twins born from 1940 to 1957 in Finland were screened for nonorganic psychotic disorder diagnoses as recorded on an inpatient or outpatient basis or from an eligibility review for a disability pension. <h3>Results</h3> The lifetime prevalence of schizophrenia was 2.0%, with a marginally higher prevalence in men (2.2%) than women (1.8%). Model fitting indicated that 83% of the variance in liability was due to additive genetic factors, and the remaining 17% was due to unique environmental factors. Sex-limitation modeling revealed no evidence of sex-specific genetic effects and no sex difference in the magnitude of heritability. A multiple threshold model incorporating affective and other psychoses as a phenotype intermediate between schizophrenia and no diagnosis was rejected. <h3>Conclusions</h3> In a population-based twin study of schizophrenia, heritability was estimated at 83%, with the remaining variance in liability attributed to environmental factors not shared in common among co-twins. Despite the notable limitation of using diagnoses ascertained through treatment contacts, the heritability estimate in this study is almost identical to those reported in recent studies of index pairs using standardized applications of<i>DSM-III</i>or later criteria.