Stress-related exposures amplify the effects of genetic susceptibility on depression and anxiety
Abstract It is unclear whether and to what extent stress-related exposures moderate the effects of polygenic risk scores (PRSs) on depression and anxiety. We aimed to examine such moderation effects for a variety of stress-related exposures on depression and anxiety. We included 41,810 participants...
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| Format: | Article |
| Language: | English |
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Nature Publishing Group
2023-01-01
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| Series: | Translational Psychiatry |
| Online Access: | https://doi.org/10.1038/s41398-023-02327-3 |
| _version_ | 1811171514145308672 |
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| author | Rujia Wang Lifelines Cohort Study Catharina A. Hartman Harold Snieder |
| author_facet | Rujia Wang Lifelines Cohort Study Catharina A. Hartman Harold Snieder |
| author_sort | Rujia Wang |
| collection | DOAJ |
| description | Abstract It is unclear whether and to what extent stress-related exposures moderate the effects of polygenic risk scores (PRSs) on depression and anxiety. We aimed to examine such moderation effects for a variety of stress-related exposures on depression and anxiety. We included 41,810 participants with both genome-wide genetic data and measurements of depression and anxiety in the Lifelines Cohort Study. Current depression and anxiety were measured by the MINI International Neuropsychiatric Interview. Stress-related exposures included long-term difficulties, stressful life events, reduced social support, childhood trauma, and loneliness, which were measured by self-report questionnaires. PRSs were calculated based on recent large genome-wide association studies for depression and anxiety. We used linear mixed models adjusting for family relationships to estimate the interactions between PRSs and stress-related exposures. Nine of the ten investigated interactions between the five stress-related exposures and the two PRSs for depression and anxiety were significant (Ps < 0.001). Reduced social support, and higher exposure to long-term difficulties, stressful life events, and loneliness amplified the genetic effects on both depression and anxiety. As for childhood trauma exposure, its interaction with the PRS was significant for depression (P = 1.78 × 10–05) but not for anxiety (P = 0.32). Higher levels of stress-related exposures significantly amplify the effects of genetic susceptibility on depression and anxiety. With a large sample size and a comprehensive set of stress-related exposures, our study provides powerful evidence on the presence of polygenic risk-by-environment interactions in relation to depression and anxiety. |
| first_indexed | 2024-04-10T17:16:18Z |
| format | Article |
| id | doaj.art-84f9bd533f6f45529eb57c632cfd6a76 |
| institution | Directory Open Access Journal |
| issn | 2158-3188 |
| language | English |
| last_indexed | 2024-04-10T17:16:18Z |
| publishDate | 2023-01-01 |
| publisher | Nature Publishing Group |
| record_format | Article |
| series | Translational Psychiatry |
| spelling | doaj.art-84f9bd533f6f45529eb57c632cfd6a762023-02-05T12:24:38ZengNature Publishing GroupTranslational Psychiatry2158-31882023-01-0113111010.1038/s41398-023-02327-3Stress-related exposures amplify the effects of genetic susceptibility on depression and anxietyRujia Wang0Lifelines Cohort StudyCatharina A. Hartman1Harold Snieder2Department of Epidemiology, University of Groningen, University Medical Center GroningenDepartment of Psychiatry, University of Groningen, University Medical Center GroningenDepartment of Epidemiology, University of Groningen, University Medical Center GroningenAbstract It is unclear whether and to what extent stress-related exposures moderate the effects of polygenic risk scores (PRSs) on depression and anxiety. We aimed to examine such moderation effects for a variety of stress-related exposures on depression and anxiety. We included 41,810 participants with both genome-wide genetic data and measurements of depression and anxiety in the Lifelines Cohort Study. Current depression and anxiety were measured by the MINI International Neuropsychiatric Interview. Stress-related exposures included long-term difficulties, stressful life events, reduced social support, childhood trauma, and loneliness, which were measured by self-report questionnaires. PRSs were calculated based on recent large genome-wide association studies for depression and anxiety. We used linear mixed models adjusting for family relationships to estimate the interactions between PRSs and stress-related exposures. Nine of the ten investigated interactions between the five stress-related exposures and the two PRSs for depression and anxiety were significant (Ps < 0.001). Reduced social support, and higher exposure to long-term difficulties, stressful life events, and loneliness amplified the genetic effects on both depression and anxiety. As for childhood trauma exposure, its interaction with the PRS was significant for depression (P = 1.78 × 10–05) but not for anxiety (P = 0.32). Higher levels of stress-related exposures significantly amplify the effects of genetic susceptibility on depression and anxiety. With a large sample size and a comprehensive set of stress-related exposures, our study provides powerful evidence on the presence of polygenic risk-by-environment interactions in relation to depression and anxiety.https://doi.org/10.1038/s41398-023-02327-3 |
| spellingShingle | Rujia Wang Lifelines Cohort Study Catharina A. Hartman Harold Snieder Stress-related exposures amplify the effects of genetic susceptibility on depression and anxiety Translational Psychiatry |
| title | Stress-related exposures amplify the effects of genetic susceptibility on depression and anxiety |
| title_full | Stress-related exposures amplify the effects of genetic susceptibility on depression and anxiety |
| title_fullStr | Stress-related exposures amplify the effects of genetic susceptibility on depression and anxiety |
| title_full_unstemmed | Stress-related exposures amplify the effects of genetic susceptibility on depression and anxiety |
| title_short | Stress-related exposures amplify the effects of genetic susceptibility on depression and anxiety |
| title_sort | stress related exposures amplify the effects of genetic susceptibility on depression and anxiety |
| url | https://doi.org/10.1038/s41398-023-02327-3 |
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