Summary: A new twin study finds that genetic factors may account for as much as 79% of schizophrenia risk.
Source: Elsevier
A large twin study finds strong genetic influence on schizophrenia risk
Researchers at the University of Copenhagen report in the journal Biological Psychiatry that genetic factors explain a substantial portion of schizophrenia risk. By analysing the largest twin sample ever assembled for schizophrenia research, the team estimates schizophrenia heritability at approximately 79%, providing one of the most precise estimates to date.
The study examined more than 30,000 twin pairs drawn from the nationwide Danish Twin Register and cross-referenced diagnoses with the Danish Psychiatric Central Research Register. The authors used an improved statistical approach that accounts for the fact that some individuals at risk for schizophrenia may not have developed symptoms by the end of follow-up. By adjusting for this type of censoring, the researchers reduced a source of bias that has complicated earlier heritability estimates.
Using liability-threshold models with inverse probability weighting to adjust for censoring, the team calculated probandwise concordance rates and heritability for both narrowly defined schizophrenia and a broader schizophrenia-spectrum outcome. The probandwise concordance rate for schizophrenia was 33% in monozygotic (identical) twins and 7% in dizygotic (fraternal) twins. From these data the study derived a heritability estimate of 79% for schizophrenia. When the researchers expanded the outcome to include schizophrenia-spectrum disorders, the estimated heritability was 73%—a value similar to the narrow definition and consistent with a strong genetic contribution across the illness spectrum.
Dr. Rikke Hilker and colleagues note that while the high heritability underscores the importance of genetic risk, the 33% concordance rate among monozygotic twins also highlights a major role for non-genetic factors and individual-specific influences. In other words, shared genetics substantially increase vulnerability, but genetics alone do not determine who will develop the illness.
John Krystal, Editor of Biological Psychiatry, observed that the new 79% heritability estimate aligns with the upper range of previous twin-based estimates (historically reported between approximately 50% and 80%). The improved precision in this study derives from both the exceptional size of the nationwide twin sample and the application of statistical methods that explicitly account for follow-up censoring, making these findings one of the most comprehensive assessments of schizophrenia heritability to date.
Why the broader spectrum matters
The authors emphasise that schizophrenia can present with a wide range of clinical features, from severe, persistent symptoms and lifelong disability to more subtle or transient psychotic phenomena. By estimating heritability for both strict diagnostic criteria and a broader spectrum that includes related disorders, the study shows that the genetic contribution is not confined to a narrow case definition but extends across the broader phenotype. This suggests that efforts to identify risk genes and biological pathways should consider the wider array of schizophrenia-related presentations.
Study design and strengths
The study combined two comprehensive national registries to create a cohort of 31,524 twin pairs born between 1951 and 2000, with follow-up through June 1, 2011. The key methodological advance was the use of liability-threshold models that adjust for censoring in the follow-up period via inverse probability weighting. This approach reduces misclassification that occurs when individuals classified as unaffected later develop the disorder, a limitation in many prior heritability studies.
Key findings
- Probandwise concordance rate for schizophrenia: 33% in monozygotic twins, 7% in dizygotic twins.
- Estimated heritability for schizophrenia: 79%.
- Estimated heritability for schizophrenia-spectrum disorders: 73%.
- The results indicate substantial genetic risk across both narrow and broader diagnostic definitions while underscoring that genetics is not the sole determinant of illness.
About the research
The peer-reviewed research article is titled “Heritability of Schizophrenia and Schizophrenia Spectrum Based on the Nationwide Danish Twin Register.” It was authored by Rikke Hilker, Dorte Helenius, Birgitte Fagerlund, Axel Skytthe, Kaare Christensen, Thomas M. Werge, Merete Nordentoft, and Birte Glenthøj, and published online in Biological Psychiatry on August 30, 2017 (doi:10.1016/j.biopsych.2017.08.017). The study used nationwide Danish registry data and advanced statistical techniques to provide updated and robust heritability estimates.
Conclusions
This comprehensive twin study supports a major role for genetic factors in schizophrenia risk while also highlighting important non-genetic contributions: even identical twins show only partial concordance. The findings strengthen the rationale for continued genetic research into schizophrenia and suggest that investigations should account for diagnostic diversity across the schizophrenia spectrum.