Summary: A new study reveals schizophrenia is up to 79% hereditary.

Source: Elsevier.

A new study in Biological Psychiatry looks at the risk for schizophrenia in twins.

In the largest study of twins in schizophrenia research to date, researchers at the University of Copenhagen, Denmark, estimate that as much as 79% of schizophrenia risk may be explained by genetic factors. The estimate indicates that genetics have a substantial influence on risk for the disorder.

Published in Biological Psychiatry, the study used a new statistical approach to address one of the factors that contributes to inconsistencies across previous studies-usually studies of heritability require that people be classified as either having schizophrenia or not, but some people at risk could still develop the disease after the study ends. Drs. Hilker, Helenius and colleagues applied a new method to take this problem into account, making the current estimates likely the most accurate to date.

“The new estimate of heritability of schizophrenia, 79%, is very close to the high end of prior estimates of its heritability,” said Dr. John Krystal, Editor of Biological Psychiatry, referring to previous estimates that have varied between 50% and 80%. “It supports the intensive efforts in place to try to identify the genes contributing to the risk for developing schizophrenia,” said Dr. Krystal, which have been built on the idea that schizophrenia is highly heritable based on the findings of generations of twin studies.

The study took advantage of the nationwide Danish Twin Register-a record of all twins born in Denmark since 1870-coupled with information from the Danish Psychiatric Central Research Register, to assess genetic liability in over 30,000 pairs of twins.

Because the diagnosis of schizophrenia is based on a narrow definition of symptoms, the researchers also estimated heritability using a broader illness category including related disorders on the schizophrenia spectrum. They found a similar estimate of 73%, indicating the importance of genetic factors across the full illness spectrum.

Dr. Hilker explained, “This study is now the most comprehensive and thorough estimate of the heritability of schizophrenia and its diagnostic diversity. It is interesting since it indicates that the genetic risk for disease seems to be of almost equal importance across the spectrum of schizophrenia,” even though the clinical presentation may range from severe symptoms with lifelong disability to more subtle and transient symptoms. “Hence, genetic risk seems not restricted to a narrow illness definition, but instead includes a broader diagnostic profile,” she added.

Source: Elsevier
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Original Research: Full open access research for “Heritability of Schizophrenia and Schizophrenia Spectrum Based on the Nationwide Danish Twin Register” by Rikke Hilker, Dorte Helenius, Birgitte Fagerlund, Axel Skytthe, Kaare Christensen, Thomas M. Werge, Merete Nordentoft, and Birte Glenthøj in Biological Psychiatry. Published online August 30 2017 doi:10.1016/j.biopsych.2017.08.017

Abstract

Heritability of Schizophrenia and Schizophrenia Spectrum Based on the Nationwide Danish Twin Register

Background
Twin studies have provided evidence that both genetic and environmental factors contribute to schizophrenia (SZ) risk. Heritability estimates of SZ in twin samples have varied methodologically. This study provides updated heritability estimates based on nationwide twin data and an improved statistical methodology.

Methods
Combining two nationwide registers, the Danish Twin Register and the Danish Psychiatric Research Register, we identified a sample of twins born between 1951 and 2000 (N = 31,524 twin pairs). Twins were followed until June 1, 2011. Liability threshold models adjusting for censoring with inverse probability weighting were used to estimate probandwise concordance rates and heritability of the diagnoses of SZ and SZ spectrum disorders.

Results
The probandwise concordance rate of SZ is 33% in monozygotic twins and 7% in dizygotic twins. We estimated the heritability of SZ to be 79%. When expanding illness outcome to include SZ spectrum disorders, the heritability estimate was almost similar (73%).

Conclusions
The key strength of this study is the application of a novel statistical method accounting for censoring in the follow-up period to a nationwide twin sample. The estimated 79% heritability of SZ is congruent with previous reports and indicates a substantial genetic risk. The high genetic risk also applies to a broader phenotype of SZ spectrum disorders. The low concordance rate of 33% in monozygotic twins demonstrates that illness vulnerability is not solely indicated by genetic factors.

“Heritability of Schizophrenia and Schizophrenia Spectrum Based on the Nationwide Danish Twin Register” by Rikke Hilker, Dorte Helenius, Birgitte Fagerlund, Axel Skytthe, Kaare Christensen, Thomas M. Werge, Merete Nordentoft, and Birte Glenthøj in Biological Psychiatry. Published online August 30 2017 doi:10.1016/j.biopsych.2017.08.017