Heritability and polygenic load for comorbid anxiety and depression

Fara Tabrizi; Jörgen Rosén; Hampus Grönvall; Victor Rahimzadeh William-Olsson; Erik Arner; Patrik Ke Magnusson; Camilla Palm; Henrik Larsson; Alexander Viktorin; Jens Bernhardsson; Johanna Björkdahl; Billy Jansson; Örjan Sundin; Xuan Zhou; Doug Speed; Fredrik Åhs

doi:10.1038/s41398-025-03325-3

Heritability and polygenic load for comorbid anxiety and depression

Fara Tabrizi, Jörgen Rosén, Hampus Grönvall, Victor Rahimzadeh William-Olsson, Erik Arner, Patrik Ke Magnusson, Camilla Palm, Henrik Larsson, Alexander Viktorin, Jens Bernhardsson, Johanna Björkdahl, Billy Jansson, Örjan Sundin, Xuan Zhou, Doug Speed, Fredrik Åhs

Center for Quantitative Genetics and Genomics

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

1 Citation (Scopus)

Abstract

Anxiety and depression commonly occur together resulting in worse health outcomes than when they occur in isolation. We aimed to determine whether the genetic liability for comorbid anxiety and depression was greater than when anxiety or depression occurred alone. Data from 12,792 genotyped twins (ages 38-85) were analysed, including 1,986 complete monozygotic and 1,594 complete dizygotic pairs. Outcomes were prescription of antidepressant and anxiolytic drugs, as defined by the World Health Organization Anatomical Therapeutic Chemical Classification System (ATC) convention, for comorbid anxiety and depression (n = 1028), anxiety only (n = 718), and depression only (n = 484). Heritability of each outcome was estimated using twin modelling, and the influence of common genetic variation was assessed from polygenic scores (PGS) for depressive symptoms, anxiety, and 40 other traits. Heritability of comorbid anxiety and depression was 79% compared with 41% for anxiety and 50% for depression alone. The PGS for depressive symptoms likewise predicted more variation in comorbid anxiety and depression (adjusted odds ratio per SD PGS = 1.53, 95% CI = 1.43-1.63; ΔR 2 = 0.031, ΔAUC = 0.044) than the other outcomes, with nearly identical results when comorbid anxiety and depression was defined by International Classification of Diseases (ICD) diagnoses (adjusted odds ratio per SD PGS = 1.70, 95% CI = 1.53-1.90; ΔR 2 = 0.036, ΔAUC = 0.051). Individuals in the highest decile of PGS for depressive symptoms had over 5 times higher odds of being prescribed medication for comorbid anxiety and depression compared to those in the lowest decile. While results on a predominant role of depressive symptoms may have been biased by the size and heterogeneity of available data bases, they are consistent with the conclusion that genetic factors explain substantially more variation in comorbid anxiety and depression than anxiety or depression alone.

Original language	English
Article number	98
Journal	Translational Psychiatry
Volume	15
Issue	1
Pages (from-to)	98
Number of pages	10
ISSN	2158-3188
DOIs	https://doi.org/10.1038/s41398-025-03325-3
Publication status	Published - Dec 2025

Keywords

Humans
Male
Female
Middle Aged
Multifactorial Inheritance
Comorbidity
Adult
Aged
Aged, 80 and over
Twins, Monozygotic/genetics
Anxiety Disorders/genetics
Depression/genetics
Anxiety/genetics
Twins, Dizygotic/genetics
Genetic Predisposition to Disease
Antidepressive Agents/therapeutic use
Anti-Anxiety Agents/therapeutic use
Depressive Disorder/genetics
Diseases in Twins/genetics

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Tabrizi, F., Rosén, J., Grönvall, H., William-Olsson, V. R., Arner, E., Magnusson, P. K., Palm, C., Larsson, H., Viktorin, A., Bernhardsson, J., Björkdahl, J., Jansson, B., Sundin, Ö., Zhou, X., Speed, D., & Åhs, F. (2025). Heritability and polygenic load for comorbid anxiety and depression. Translational Psychiatry, 15(1), 98. Article 98. https://doi.org/10.1038/s41398-025-03325-3

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abstract = "Anxiety and depression commonly occur together resulting in worse health outcomes than when they occur in isolation. We aimed to determine whether the genetic liability for comorbid anxiety and depression was greater than when anxiety or depression occurred alone. Data from 12,792 genotyped twins (ages 38-85) were analysed, including 1,986 complete monozygotic and 1,594 complete dizygotic pairs. Outcomes were prescription of antidepressant and anxiolytic drugs, as defined by the World Health Organization Anatomical Therapeutic Chemical Classification System (ATC) convention, for comorbid anxiety and depression (n = 1028), anxiety only (n = 718), and depression only (n = 484). Heritability of each outcome was estimated using twin modelling, and the influence of common genetic variation was assessed from polygenic scores (PGS) for depressive symptoms, anxiety, and 40 other traits. Heritability of comorbid anxiety and depression was 79% compared with 41% for anxiety and 50% for depression alone. The PGS for depressive symptoms likewise predicted more variation in comorbid anxiety and depression (adjusted odds ratio per SD PGS = 1.53, 95% CI = 1.43-1.63; ΔR 2 = 0.031, ΔAUC = 0.044) than the other outcomes, with nearly identical results when comorbid anxiety and depression was defined by International Classification of Diseases (ICD) diagnoses (adjusted odds ratio per SD PGS = 1.70, 95% CI = 1.53-1.90; ΔR 2 = 0.036, ΔAUC = 0.051). Individuals in the highest decile of PGS for depressive symptoms had over 5 times higher odds of being prescribed medication for comorbid anxiety and depression compared to those in the lowest decile. While results on a predominant role of depressive symptoms may have been biased by the size and heterogeneity of available data bases, they are consistent with the conclusion that genetic factors explain substantially more variation in comorbid anxiety and depression than anxiety or depression alone. ",

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doi = "10.1038/s41398-025-03325-3",

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Tabrizi, F, Rosén, J, Grönvall, H, William-Olsson, VR, Arner, E, Magnusson, PK, Palm, C, Larsson, H, Viktorin, A, Bernhardsson, J, Björkdahl, J, Jansson, B, Sundin, Ö, Zhou, X, Speed, D & Åhs, F 2025, 'Heritability and polygenic load for comorbid anxiety and depression', Translational Psychiatry, vol. 15, no. 1, 98, pp. 98. https://doi.org/10.1038/s41398-025-03325-3

TY - JOUR

T1 - Heritability and polygenic load for comorbid anxiety and depression

AU - Tabrizi, Fara

AU - Rosén, Jörgen

AU - Grönvall, Hampus

AU - William-Olsson, Victor Rahimzadeh

AU - Arner, Erik

AU - Magnusson, Patrik Ke

AU - Palm, Camilla

AU - Larsson, Henrik

AU - Viktorin, Alexander

AU - Bernhardsson, Jens

AU - Björkdahl, Johanna

AU - Jansson, Billy

AU - Sundin, Örjan

AU - Zhou, Xuan

AU - Speed, Doug

AU - Åhs, Fredrik

PY - 2025/12

Y1 - 2025/12

N2 - Anxiety and depression commonly occur together resulting in worse health outcomes than when they occur in isolation. We aimed to determine whether the genetic liability for comorbid anxiety and depression was greater than when anxiety or depression occurred alone. Data from 12,792 genotyped twins (ages 38-85) were analysed, including 1,986 complete monozygotic and 1,594 complete dizygotic pairs. Outcomes were prescription of antidepressant and anxiolytic drugs, as defined by the World Health Organization Anatomical Therapeutic Chemical Classification System (ATC) convention, for comorbid anxiety and depression (n = 1028), anxiety only (n = 718), and depression only (n = 484). Heritability of each outcome was estimated using twin modelling, and the influence of common genetic variation was assessed from polygenic scores (PGS) for depressive symptoms, anxiety, and 40 other traits. Heritability of comorbid anxiety and depression was 79% compared with 41% for anxiety and 50% for depression alone. The PGS for depressive symptoms likewise predicted more variation in comorbid anxiety and depression (adjusted odds ratio per SD PGS = 1.53, 95% CI = 1.43-1.63; ΔR 2 = 0.031, ΔAUC = 0.044) than the other outcomes, with nearly identical results when comorbid anxiety and depression was defined by International Classification of Diseases (ICD) diagnoses (adjusted odds ratio per SD PGS = 1.70, 95% CI = 1.53-1.90; ΔR 2 = 0.036, ΔAUC = 0.051). Individuals in the highest decile of PGS for depressive symptoms had over 5 times higher odds of being prescribed medication for comorbid anxiety and depression compared to those in the lowest decile. While results on a predominant role of depressive symptoms may have been biased by the size and heterogeneity of available data bases, they are consistent with the conclusion that genetic factors explain substantially more variation in comorbid anxiety and depression than anxiety or depression alone.

AB - Anxiety and depression commonly occur together resulting in worse health outcomes than when they occur in isolation. We aimed to determine whether the genetic liability for comorbid anxiety and depression was greater than when anxiety or depression occurred alone. Data from 12,792 genotyped twins (ages 38-85) were analysed, including 1,986 complete monozygotic and 1,594 complete dizygotic pairs. Outcomes were prescription of antidepressant and anxiolytic drugs, as defined by the World Health Organization Anatomical Therapeutic Chemical Classification System (ATC) convention, for comorbid anxiety and depression (n = 1028), anxiety only (n = 718), and depression only (n = 484). Heritability of each outcome was estimated using twin modelling, and the influence of common genetic variation was assessed from polygenic scores (PGS) for depressive symptoms, anxiety, and 40 other traits. Heritability of comorbid anxiety and depression was 79% compared with 41% for anxiety and 50% for depression alone. The PGS for depressive symptoms likewise predicted more variation in comorbid anxiety and depression (adjusted odds ratio per SD PGS = 1.53, 95% CI = 1.43-1.63; ΔR 2 = 0.031, ΔAUC = 0.044) than the other outcomes, with nearly identical results when comorbid anxiety and depression was defined by International Classification of Diseases (ICD) diagnoses (adjusted odds ratio per SD PGS = 1.70, 95% CI = 1.53-1.90; ΔR 2 = 0.036, ΔAUC = 0.051). Individuals in the highest decile of PGS for depressive symptoms had over 5 times higher odds of being prescribed medication for comorbid anxiety and depression compared to those in the lowest decile. While results on a predominant role of depressive symptoms may have been biased by the size and heterogeneity of available data bases, they are consistent with the conclusion that genetic factors explain substantially more variation in comorbid anxiety and depression than anxiety or depression alone.

KW - Humans

KW - Male

KW - Female

KW - Middle Aged

KW - Multifactorial Inheritance

KW - Comorbidity

KW - Adult

KW - Aged

KW - Aged, 80 and over

KW - Twins, Monozygotic/genetics

KW - Anxiety Disorders/genetics

KW - Depression/genetics

KW - Anxiety/genetics

KW - Twins, Dizygotic/genetics

KW - Genetic Predisposition to Disease

KW - Antidepressive Agents/therapeutic use

KW - Anti-Anxiety Agents/therapeutic use

KW - Depressive Disorder/genetics

KW - Diseases in Twins/genetics

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U2 - 10.1038/s41398-025-03325-3

DO - 10.1038/s41398-025-03325-3

M3 - Journal article

C2 - 40140358

SN - 2158-3188

VL - 15

SP - 98

JO - Translational Psychiatry

JF - Translational Psychiatry

IS - 1

M1 - 98

ER -

Heritability and polygenic load for comorbid anxiety and depression

Abstract

Keywords

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