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

Katherine L Musliner; Klaus K Andersen; Esben Agerbo; Clara Albiñana; Bjarni J Vilhjalmsson; Veera M Rajagopal; Jonas Bybjerg-Grauholm; Marie Bækved-Hansen; Carsten B Pedersen; Marianne G Pedersen; Trine Munk-Olsen; Michael E Benros; Thomas D Als; Jakob Grove; Thomas Werge; Anders D Børglum; David M Hougaard; Ole Mors; Merete Nordentoft; Preben B Mortensen; Nis P Suppli; Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium

doi:10.1017/S0033291721001410

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

Katherine L Musliner, Klaus K Andersen, Esben Agerbo, Clara Albiñana, Bjarni J Vilhjalmsson, Veera M Rajagopal, Jonas Bybjerg-Grauholm, Marie Bækved-Hansen, Carsten B Pedersen, Marianne G Pedersen, Trine Munk-Olsen, Michael E Benros, Thomas D Als, Jakob Grove, Thomas Werge, Anders D Børglum, David M Hougaard, Ole Mors, Merete Nordentoft, Preben B MortensenNis P Suppli, Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaper › Journal article › Research › peer-review

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.

Original language	English
Journal	Psychological Medicine
Volume	53
Issue	1
Pages (from-to)	217-226
Number of pages	10
ISSN	0033-2917
DOIs	https://doi.org/10.1017/S0033291721001410
Publication status	Published - Jan 2023

Keywords

Absolute risk
case-cohort study
depression
interaction
polygenic risk scores
stressful life events

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10.1017/S0033291721001410

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Musliner, K. L., Andersen, K. K., Agerbo, E., Albiñana, C., Vilhjalmsson, B. J., Rajagopal, V. M., Bybjerg-Grauholm, J., Bækved-Hansen, M., Pedersen, C. B., Pedersen, M. G., Munk-Olsen, T., Benros, M. E., Als, T. D., Grove, J., Werge, T., Børglum, A. D., Hougaard, D. M., Mors, O., Nordentoft, M., ... Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium (2023). Polygenic liability, stressful life events and risk for secondary-treated depression in early life: a nationwide register-based case-cohort study. Psychological Medicine, 53(1), 217-226. https://doi.org/10.1017/S0033291721001410

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

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 risk, case-cohort study, depression, interaction, polygenic risk scores, stressful life events",

author = "Musliner, {Katherine L} and Andersen, {Klaus K} and Esben Agerbo and Clara Albi{\~n}ana and Vilhjalmsson, {Bjarni J} and Rajagopal, {Veera M} and Jonas Bybjerg-Grauholm and Marie B{\ae}kved-Hansen and Pedersen, {Carsten B} and Pedersen, {Marianne G} and Trine Munk-Olsen and Benros, {Michael E} and Als, {Thomas D} and Jakob Grove and Thomas Werge and B{\o}rglum, {Anders D} and Hougaard, {David M} and Ole Mors and Merete Nordentoft and Mortensen, {Preben B} and Suppli, {Nis P} and {Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium} and Christensen, {Jane H.}",

year = "2023",

month = jan,

doi = "10.1017/S0033291721001410",

language = "English",

volume = "53",

pages = "217--226",

journal = "Psychological Medicine",

issn = "0033-2917",

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Musliner, KL, Andersen, KK, Agerbo, E , Albiñana, C , Vilhjalmsson, BJ, Rajagopal, VM, Bybjerg-Grauholm, J, Bækved-Hansen, M, Pedersen, CB , Pedersen, MG , Munk-Olsen, T, Benros, ME, Als, TD , Grove, J, Werge, T, Børglum, AD, Hougaard, DM, Mors, O, Nordentoft, M, Mortensen, PB, Suppli, NP & Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium 2023, 'Polygenic liability, stressful life events and risk for secondary-treated depression in early life: a nationwide register-based case-cohort study', Psychological Medicine, vol. 53, no. 1, pp. 217-226. https://doi.org/10.1017/S0033291721001410

Polygenic liability, stressful life events and risk for secondary-treated depression in early life: a nationwide register-based case-cohort study. / Musliner, Katherine L; Andersen, Klaus K; Agerbo, Esben et al.
In: Psychological Medicine, Vol. 53, No. 1, 01.2023, p. 217-226.

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaper › Journal article › Research › peer-review

TY - JOUR

T1 - Polygenic liability, stressful life events and risk for secondary-treated depression in early life

T2 - a nationwide register-based case-cohort study

AU - Musliner, Katherine L

AU - Andersen, Klaus K

AU - Agerbo, Esben

AU - Albiñana, Clara

AU - Vilhjalmsson, Bjarni J

AU - Rajagopal, Veera M

AU - Bybjerg-Grauholm, Jonas

AU - Bækved-Hansen, Marie

AU - Pedersen, Carsten B

AU - Pedersen, Marianne G

AU - Munk-Olsen, Trine

AU - Benros, Michael E

AU - Als, Thomas D

AU - Grove, Jakob

AU - Werge, Thomas

AU - Børglum, Anders D

AU - Hougaard, David M

AU - Mors, Ole

AU - Nordentoft, Merete

AU - Mortensen, Preben B

AU - Suppli, Nis P

AU - Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium

AU - Christensen, Jane H.

PY - 2023/1

Y1 - 2023/1

N2 - 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.

AB - 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.

KW - Absolute risk

KW - case-cohort study

KW - depression

KW - interaction

KW - polygenic risk scores

KW - stressful life events

U2 - 10.1017/S0033291721001410

DO - 10.1017/S0033291721001410

M3 - Journal article

C2 - 33949298

SN - 0033-2917

VL - 53

SP - 217

EP - 226

JO - Psychological Medicine

JF - Psychological Medicine

IS - 1

ER -

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

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Keywords

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