Department of Economics and Business Economics

Manuel Mattheisen

Association of the polygenic risk score for schizophrenia with mortality and suicidal behavior - A Danish population-based study

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Association of the polygenic risk score for schizophrenia with mortality and suicidal behavior - A Danish population-based study. / Laursen, Thomas M; Trabjerg, Betina B; Mors, Ole; Børglum, Anders D; Hougaard, David M; Mattheisen, Manuel; Meier, Sandra M; Byrne, Enda M; Mortensen, Preben B; Munk-Olsen, Trine; Agerbo, Esben.

In: Schizophrenia Research, Vol. 184, 2017, p. 122-127.

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@article{a94f253e579a49d7b236364670ae6a33,
title = "Association of the polygenic risk score for schizophrenia with mortality and suicidal behavior - A Danish population-based study",
abstract = "BACKGROUND: It is unknown whether an increased genetic liability to schizophrenia influences the risk of dying early. The aim of the study was to determine whether the genetic predisposition to schizophrenia is associated with the risk of dying early and experience a suicide attempt.METHOD: Case control study, Denmark. The main measure was the mortality rate ratios (MRR) for deaths and odds ratios (OR) for multiple suicide attempts, associated with one standard deviations increase of the polygenic risk-score for schizophrenia (PRS).RESULTS: We replicated the high mortality MRR=9.01 (95% CI: 3.56-22.80), and high risk of multiple suicide attempts OR=33.16 (95% CI: 20.97-52.43) associated with schizophrenia compared to the general population. However, there was no effect of the PRS on mortality MRR=1.00 (95% CI 0.71-1.40) in the case-control setup or in cases only, MRR=1.05 (95% CI 0.73-1.51). Similar, no association between the PRS and multiple suicide attempts was found in the adjusted models, but in contrast, family history of mental disorders was associated with both outcomes.CONCLUSIONS: A genetic predisposition for schizophrenia, measured by PRS, has little influence on the excess mortality or the risk of suicide attempts. In contrast there is a strong significant effect of family history of mental disorders. Our findings could reflect that the common variants detected by recent PRS only explain a small proportion of risk of schizophrenia, and that future, more powerful PRS instruments may be able to predict excess mortality within this disorder.",
keywords = "Adolescent, Adult, Biological Specimen Banks, Case-Control Studies, Denmark/epidemiology, Female, Genetic Predisposition to Disease, Humans, Male, Mortality, Premature, Multifactorial Inheritance, Registries, Risk, Schizophrenia/genetics, Suicide, Attempted/statistics & numerical data, Young Adult",
author = "Laursen, {Thomas M} and Trabjerg, {Betina B} and Ole Mors and B{\o}rglum, {Anders D} and Hougaard, {David M} and Manuel Mattheisen and Meier, {Sandra M} and Byrne, {Enda M} and Mortensen, {Preben B} and Trine Munk-Olsen and Esben Agerbo",
note = "Copyright {\textcopyright} 2016. Published by Elsevier B.V.",
year = "2017",
doi = "10.1016/j.schres.2016.12.001",
language = "English",
volume = "184",
pages = "122--127",
journal = "Schizophrenia Research",
issn = "0920-9964",
publisher = "Elsevier BV",

}

RIS

TY - ABST

T1 - Association of the polygenic risk score for schizophrenia with mortality and suicidal behavior - A Danish population-based study

AU - Laursen, Thomas M

AU - Trabjerg, Betina B

AU - Mors, Ole

AU - Børglum, Anders D

AU - Hougaard, David M

AU - Mattheisen, Manuel

AU - Meier, Sandra M

AU - Byrne, Enda M

AU - Mortensen, Preben B

AU - Munk-Olsen, Trine

AU - Agerbo, Esben

N1 - Copyright © 2016. Published by Elsevier B.V.

PY - 2017

Y1 - 2017

N2 - BACKGROUND: It is unknown whether an increased genetic liability to schizophrenia influences the risk of dying early. The aim of the study was to determine whether the genetic predisposition to schizophrenia is associated with the risk of dying early and experience a suicide attempt.METHOD: Case control study, Denmark. The main measure was the mortality rate ratios (MRR) for deaths and odds ratios (OR) for multiple suicide attempts, associated with one standard deviations increase of the polygenic risk-score for schizophrenia (PRS).RESULTS: We replicated the high mortality MRR=9.01 (95% CI: 3.56-22.80), and high risk of multiple suicide attempts OR=33.16 (95% CI: 20.97-52.43) associated with schizophrenia compared to the general population. However, there was no effect of the PRS on mortality MRR=1.00 (95% CI 0.71-1.40) in the case-control setup or in cases only, MRR=1.05 (95% CI 0.73-1.51). Similar, no association between the PRS and multiple suicide attempts was found in the adjusted models, but in contrast, family history of mental disorders was associated with both outcomes.CONCLUSIONS: A genetic predisposition for schizophrenia, measured by PRS, has little influence on the excess mortality or the risk of suicide attempts. In contrast there is a strong significant effect of family history of mental disorders. Our findings could reflect that the common variants detected by recent PRS only explain a small proportion of risk of schizophrenia, and that future, more powerful PRS instruments may be able to predict excess mortality within this disorder.

AB - BACKGROUND: It is unknown whether an increased genetic liability to schizophrenia influences the risk of dying early. The aim of the study was to determine whether the genetic predisposition to schizophrenia is associated with the risk of dying early and experience a suicide attempt.METHOD: Case control study, Denmark. The main measure was the mortality rate ratios (MRR) for deaths and odds ratios (OR) for multiple suicide attempts, associated with one standard deviations increase of the polygenic risk-score for schizophrenia (PRS).RESULTS: We replicated the high mortality MRR=9.01 (95% CI: 3.56-22.80), and high risk of multiple suicide attempts OR=33.16 (95% CI: 20.97-52.43) associated with schizophrenia compared to the general population. However, there was no effect of the PRS on mortality MRR=1.00 (95% CI 0.71-1.40) in the case-control setup or in cases only, MRR=1.05 (95% CI 0.73-1.51). Similar, no association between the PRS and multiple suicide attempts was found in the adjusted models, but in contrast, family history of mental disorders was associated with both outcomes.CONCLUSIONS: A genetic predisposition for schizophrenia, measured by PRS, has little influence on the excess mortality or the risk of suicide attempts. In contrast there is a strong significant effect of family history of mental disorders. Our findings could reflect that the common variants detected by recent PRS only explain a small proportion of risk of schizophrenia, and that future, more powerful PRS instruments may be able to predict excess mortality within this disorder.

KW - Adolescent

KW - Adult

KW - Biological Specimen Banks

KW - Case-Control Studies

KW - Denmark/epidemiology

KW - Female

KW - Genetic Predisposition to Disease

KW - Humans

KW - Male

KW - Mortality, Premature

KW - Multifactorial Inheritance

KW - Registries

KW - Risk

KW - Schizophrenia/genetics

KW - Suicide, Attempted/statistics & numerical data

KW - Young Adult

UR - http://www.scopus.com/inward/record.url?scp=85007570735&partnerID=8YFLogxK

U2 - 10.1016/j.schres.2016.12.001

DO - 10.1016/j.schres.2016.12.001

M3 - Conference abstract in journal

C2 - 27939829

VL - 184

SP - 122

EP - 127

JO - Schizophrenia Research

JF - Schizophrenia Research

SN - 0920-9964

ER -