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Polygenic liability, stressful life events and risk for secondary-treated depression in early life: a nationwide register-based case-cohort study

Published online by Cambridge University Press:  05 May 2021

Katherine L. Musliner Open the ORCID record for Katherine L. Musliner [Opens in a new window] ,
Klaus K. Andersen ,
Esben Agerbo ,
Clara Albiñana ,
Bjarni J. Vilhjalmsson ,
Veera M. Rajagopal ,
Jonas Bybjerg-Grauholm ,
Marie Bækved-Hansen ,
Carsten B. Pedersen  and
Marianne G. Pedersen
...Show all authors
Katherine L. Musliner*
Affiliation:
The Lundbeck Foundation Initiative for Integrative Psychiatric Research (iPSYCH), Aarhus, Denmark National Center for Register-based Research, Department of Economics, Aarhus University, Aarhus, Denmark
Klaus K. Andersen
Affiliation:
Unit for Statistics and Pharmacoepidemiology (SPE), Danish Cancer Society Research Center (DCRC), Copenhagen, Denmark
Esben Agerbo
Affiliation:
The Lundbeck Foundation Initiative for Integrative Psychiatric Research (iPSYCH), Aarhus, Denmark National Center for Register-based Research, Department of Economics, Aarhus University, Aarhus, Denmark The Center for Integrated Register-based Research at Aarhus University (CIRRAU), Aarhus, Denmark
Clara Albiñana
Affiliation:
The Lundbeck Foundation Initiative for Integrative Psychiatric Research (iPSYCH), Aarhus, Denmark National Center for Register-based Research, Department of Economics, Aarhus University, Aarhus, Denmark
Bjarni J. Vilhjalmsson
Affiliation:
The Lundbeck Foundation Initiative for Integrative Psychiatric Research (iPSYCH), Aarhus, Denmark National Center for Register-based Research, Department of Economics, Aarhus University, Aarhus, Denmark Bioinformatics Research Centre (BiRC), Aarhus University, Aarhus, Denmark
Veera M. Rajagopal
Affiliation:
The Lundbeck Foundation Initiative for Integrative Psychiatric Research (iPSYCH), Aarhus, Denmark Department of Biomedicine, Aarhus University, Aarhus, Denmark Center for Integrative Sequencing, iSEQ, Aarhus University, Aarhus, Denmark Center for Genome Analysis and Personalized Medicine, Aarhus, Denmark
Jonas Bybjerg-Grauholm
Affiliation:
The Lundbeck Foundation Initiative for Integrative Psychiatric Research (iPSYCH), Aarhus, Denmark Department for Congenital Disorders, Statens Serum Institute, Copenhagen, Denmark
Marie Bækved-Hansen
Affiliation:
The Lundbeck Foundation Initiative for Integrative Psychiatric Research (iPSYCH), Aarhus, Denmark Department for Congenital Disorders, Statens Serum Institute, Copenhagen, Denmark
Carsten B. Pedersen
Affiliation:
The Lundbeck Foundation Initiative for Integrative Psychiatric Research (iPSYCH), Aarhus, Denmark National Center for Register-based Research, Department of Economics, Aarhus University, Aarhus, Denmark The Center for Integrated Register-based Research at Aarhus University (CIRRAU), Aarhus, Denmark
Marianne G. Pedersen
Affiliation:
The Lundbeck Foundation Initiative for Integrative Psychiatric Research (iPSYCH), Aarhus, Denmark National Center for Register-based Research, Department of Economics, Aarhus University, Aarhus, Denmark The Center for Integrated Register-based Research at Aarhus University (CIRRAU), Aarhus, Denmark
Trine Munk-Olsen
Affiliation:
The Lundbeck Foundation Initiative for Integrative Psychiatric Research (iPSYCH), Aarhus, Denmark National Center for Register-based Research, Department of Economics, Aarhus University, Aarhus, Denmark
Michael E. Benros
Affiliation:
The Lundbeck Foundation Initiative for Integrative Psychiatric Research (iPSYCH), Aarhus, Denmark Mental Health Center Copenhagen, Copenhagen University Hospital, Copenhagen, Denmark
Thomas D. Als
Affiliation:
The Lundbeck Foundation Initiative for Integrative Psychiatric Research (iPSYCH), Aarhus, Denmark Department of Biomedicine, Aarhus University, Aarhus, Denmark
Jakob Grove
Affiliation:
The Lundbeck Foundation Initiative for Integrative Psychiatric Research (iPSYCH), Aarhus, Denmark Bioinformatics Research Centre (BiRC), Aarhus University, Aarhus, Denmark Department of Biomedicine, Aarhus University, Aarhus, Denmark Center for Genome Analysis and Personalized Medicine, Aarhus, Denmark
Thomas Werge
Affiliation:
The Lundbeck Foundation Initiative for Integrative Psychiatric Research (iPSYCH), Aarhus, Denmark Institute of Biological Psychiatry, Copenhagen Mental Health Services, Copenhagen, Denmark
Anders D. Børglum
Affiliation:
The Lundbeck Foundation Initiative for Integrative Psychiatric Research (iPSYCH), Aarhus, Denmark Department of Biomedicine, Aarhus University, Aarhus, Denmark Center for Integrative Sequencing, iSEQ, Aarhus University, Aarhus, Denmark
David M. Hougaard
Affiliation:
The Lundbeck Foundation Initiative for Integrative Psychiatric Research (iPSYCH), Aarhus, Denmark Department for Congenital Disorders, Statens Serum Institute, Copenhagen, Denmark
Ole Mors
Affiliation:
The Lundbeck Foundation Initiative for Integrative Psychiatric Research (iPSYCH), Aarhus, Denmark Psychosis Research Unit, Aarhus University Hospital-Psychiatry, Aarhus, Denmark
Merete Nordentoft
Affiliation:
The Lundbeck Foundation Initiative for Integrative Psychiatric Research (iPSYCH), Aarhus, Denmark Mental Health Center Copenhagen, Copenhagen University Hospital, Copenhagen, Denmark
Preben B. Mortensen
Affiliation:
The Lundbeck Foundation Initiative for Integrative Psychiatric Research (iPSYCH), Aarhus, Denmark National Center for Register-based Research, Department of Economics, Aarhus University, Aarhus, Denmark The Center for Integrated Register-based Research at Aarhus University (CIRRAU), Aarhus, Denmark
Nis P. Suppli
Affiliation:
The Lundbeck Foundation Initiative for Integrative Psychiatric Research (iPSYCH), Aarhus, Denmark Mental Health Center Copenhagen, Copenhagen University Hospital, Copenhagen, Denmark
*
Author for correspondence: Katherine L. Musliner, E-mail: klm@econ.au.dk
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Abstract

Background

In this study, we examined the relationship between polygenic liability for depression and number of stressful life events (SLEs) as risk factors for early-onset depression treated in inpatient, outpatient or emergency room settings at psychiatric hospitals in Denmark.

Methods

Data were drawn from the iPSYCH2012 case-cohort sample, a population-based sample of individuals born in Denmark between 1981 and 2005. The sample included 18 532 individuals who were diagnosed with depression by a psychiatrist by age 31 years, and a comparison group of 20 184 individuals. Information on SLEs was obtained from nationwide registers and operationalized as a time-varying count variable. Hazard ratios and cumulative incidence rates were estimated using Cox regressions.

Results

Risk for depression increased by 35% with each standard deviation increase in polygenic liability (p < 0.0001), and 36% (p < 0.0001) with each additional SLE. There was a small interaction between polygenic liability and SLEs (β = −0.04, p = 0.0009). The probability of being diagnosed with depression in a hospital-based setting between ages 15 and 31 years ranged from 1.5% among males in the lowest quartile of polygenic liability with 0 events by age 15, to 18.8% among females in the highest quartile of polygenic liability with 4+ events by age 15.

Conclusions

These findings suggest that although there is minimal interaction between polygenic liability and SLEs as risk factors for hospital-treated depression, combining information on these two important risk factors could potentially be useful for identifying high-risk individuals.

Keywords

Absolute riskcase-cohort studydepressioninteractionpolygenic risk scoresstressful life events
Type
Original Article
Information
Psychological Medicine , Volume 53 , Issue 1 , January 2023 , pp. 217 - 226
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Copyright
Copyright © The Author(s), 2021. Published by Cambridge University Press

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