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A Danish Twin Study of Schizophrenia Liability: Investigation from Interviewed Twins for Genetic Links to Affective Psychoses and for Cross-Cohort Comparisons

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Abstract

We studied schizophrenia liability in a Danish population-based sample of 44 twin pairs (13 MZ, 31 DZ, SS plus OS) in order to replicate previous twin study findings using contemporary diagnostic criteria, to examine genetic liability shared between schizophrenia and other disorders, and to explore whether variance in schizophrenia liability attributable to environmental factors may have decreased with successive cohorts exposed to improvements in public health. ICD-10 diagnoses were determined by clinical interview. Although the best-fitting, most parsimonious biometric model of schizophrenia liability specified variance attributable to additive genetic and non-shared environmental factors, this model did not differ significantly from a model that also included non-additive genetic factors, consistent with recent interview-based twin studies. Schizophrenia showed strong genetic links to other psychotic disorders but much less so for the broader category of psychiatric disorders in general. We also observed a marginally significant decline in schizophrenia variance attributable to environmental factors over successive Western European cohorts, consistent perhaps with improvements in diagnosis and in prenatal and perinatal care and with a secular decline in the prevalence of schizophrenia in that region.

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Acknowledgments

The authors wish to thank Christin Sindballe,, M.D, Psychiatric Center Bispebjerg, Copenhagen, for interviewing the cotwins. We are grateful for the helpful comments on earlier versions of this report from Alastair Cardno and Nick Martin and on the current version from Michael Lyons, Greg Carey, Matt McGue, and anonymous reviewers.

Funding

This work was supported by Sygekassernes Helsefond, Forskerakademiet, Forskningsinitiativet under Århus University; the Theodore and Vada Stanley Foundation, Fonden til Forskning af Sindslidelse, Fonden til Psykiatriens Fremme (Petra & Cris Andersens Fond) and Eli Lilly Denmark AIS; and a Vassar College study leave to SLT. IIG was supported by the Lieber Prize for Schizophrenia Research and the University of Louisville Grawemeyer Award in Psychology.

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Authors and Affiliations

  1. Aarhus University Hospital, Risskov, Denmark

    Ulla Kläning

  2. Department of Psychology, Vassar College, Poughkeepsie, NY, USA

    Susan L. Trumbetta

  3. Department of Psychology, University of Minnesota, 75 East River Parkway, Minneapolis, MN, 55455, USA

    Irving I. Gottesman

  4. Epidemiology, Biostatistics and Biodemography, The Danish Twin Register, University of Southern Denmark, Odense, Denmark

    Axel Skytthe

  5. Department of Clinical Research, University of Southern Denmark, Odense, Denmark

    Kirsten O. Kyvik

  6. Translational Neuropsychiatry Unit, Department of Clinical Medicine, Aarhus University, Psychiatric Hospital, Risskov, Denmark

    Aksel Bertelsen

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  1. Ulla Kläning
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  3. Irving I. Gottesman
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Correspondence to Irving I. Gottesman.

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Conflict of Interest

Ulla Kläning, Susan L. Trumbetta, Irving I. Gottesman, Axel Skytthe, Kirsten O. Kyvik, and Aksel Bertelsen declare that they have no conflict of interest.

Human and Animal Rights and Informed Consent

All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration of 1975, as revised in 2000 (5). Informed consent was obtained from all patients for being included in the study.

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Kläning, U., Trumbetta, S.L., Gottesman, I.I. et al. A Danish Twin Study of Schizophrenia Liability: Investigation from Interviewed Twins for Genetic Links to Affective Psychoses and for Cross-Cohort Comparisons. Behav Genet 46, 193–204 (2016). https://doi.org/10.1007/s10519-015-9765-z

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