The association between family history and genomic burden with schizophrenia mortality: a Swedish population-based register and genetic sample study

Individuals with schizophrenia (SCZ) have a 2–3-fold higher risk of mortality than the general population. Heritability of mortality in psychiatric disorders has been proposed; however, few have investigated SCZ family history and genetic variation, with all-cause and specific causes of death. We ai...

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Bibliographic Details
Published in:Translational psychiatry 2021-03, Vol.11 (1), p.163-163, Article 163
Main Authors: Kowalec, Kaarina, Lu, Yi, Song, Jie, Dalman, Christina, Hultman, Christina M., Larsson, Henrik, Lichtenstein, Paul, Sullivan, Patrick F.
Format: Article
Language:English
Subjects:
631/208/212/2166
692/699/476/1799
Behavioral Sciences
Biological Psychology
Medicin och hälsovetenskap
Medicine
Medicine & Public Health
Mortality
Neurosciences
Pharmacotherapy
Population
Population-based studies
Psychiatry
Schizophrenia
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Summary:Individuals with schizophrenia (SCZ) have a 2–3-fold higher risk of mortality than the general population. Heritability of mortality in psychiatric disorders has been proposed; however, few have investigated SCZ family history and genetic variation, with all-cause and specific causes of death. We aimed to identify correlates of SCZ mortality using genetic epidemiological and genetic modelling in two samples: a Swedish national population sample and a genotyped subsample. In the Swedish national population sample followed from the first SCZ treatment contact until emigration, death or end of the follow-up, we investigated a standardised measure of SCZ family history. In a subgroup with comprehensive genetic data, we investigated the impact of common and rare genetic variation. Cox proportional hazards regression was used to estimate the association between various factors and mortality (all and specific causes). A total of 13727 SCZ cases fulfilled criteria for the population-based analyses (1268 deaths, 9.2%). The genomic subset contained 4991 cases (1353 deaths, 27.1%). Somatic mutations associated with clonal hematopoiesis with unknown drivers were associated with all-cause mortality (HR 1.77, 95% CI: 1.26–2.49). No other heritable measures were associated with all-cause mortality nor with any specific causes of death. Future studies in larger, comparable cohorts are warranted to further understand the association between hereditary measures and mortality in SCZ.
ISSN:2158-3188
2158-3188
DOI:10.1038/s41398-021-01282-1