Risk Stratification for Bipolar Disorder Using Polygenic Risk Scores Among Young High-Risk Adults
Objective: Identifying high-risk groups with an increased genetic liability for bipolar disorder (BD) will provide insights into the etiology of BD and contribute to early detection of BD. We used the BD polygenic risk score (PRS) derived from BD genome-wide association studies (GWAS) to explore how...
| Main Authors: | , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2020-10-01
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| Series: | Frontiers in Psychiatry |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fpsyt.2020.552532/full |
| _version_ | 1818269601981530112 |
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| author | Silvia Biere Thorsten M. Kranz Silke Matura Kristiyana Petrova Fabian Streit Andreas G. Chiocchetti Oliver Grimm Murielle Brum Natalie Brunkhorst-Kanaan Viola Oertel Aliaksandr Malyshau Andrea Pfennig Michael Bauer Thomas G. Schulze Sarah Kittel-Schneider Sarah Kittel-Schneider Andreas Reif |
| author_facet | Silvia Biere Thorsten M. Kranz Silke Matura Kristiyana Petrova Fabian Streit Andreas G. Chiocchetti Oliver Grimm Murielle Brum Natalie Brunkhorst-Kanaan Viola Oertel Aliaksandr Malyshau Andrea Pfennig Michael Bauer Thomas G. Schulze Sarah Kittel-Schneider Sarah Kittel-Schneider Andreas Reif |
| author_sort | Silvia Biere |
| collection | DOAJ |
| description | Objective: Identifying high-risk groups with an increased genetic liability for bipolar disorder (BD) will provide insights into the etiology of BD and contribute to early detection of BD. We used the BD polygenic risk score (PRS) derived from BD genome-wide association studies (GWAS) to explore how such genetic risk manifests in young, high-risk adults. We postulated that BD-PRS would be associated with risk factors for BD.Methods: A final sample of 185 young, high-risk German adults (aged 18–35 years) were grouped into three risk groups and compared to a healthy control group (n = 1,100). The risk groups comprised 117 cases with attention deficit hyperactivity disorder (ADHD), 45 with major depressive disorder (MDD), and 23 help-seeking adults with early recognition symptoms [ER: positive family history for BD, (sub)threshold affective symptomatology and/or mood swings, sleeping disorder]. BD-PRS was computed for each participant. Logistic regression models (controlling for sex, age, and the first five ancestry principal components) were used to assess associations of BD-PRS and the high-risk phenotypes.Results: We observed an association between BD-PRS and combined risk group status (OR = 1.48, p < 0.001), ADHD diagnosis (OR = 1.32, p = 0.009), MDD diagnosis (OR = 1.96, p < 0.001), and ER group status (OR = 1.7, p = 0.025; not significant after correction for multiple testing) compared to healthy controls.Conclusions: In the present study, increased genetic risk for BD was a significant predictor for MDD and ADHD status, but not for ER. These findings support an underlying shared risk for both MDD and BD as well as ADHD and BD. Improving our understanding of the underlying genetic architecture of these phenotypes may aid in early identification and risk stratification. |
| first_indexed | 2024-12-12T20:56:59Z |
| format | Article |
| id | doaj.art-996e3f8390b74a73bc89880171746d45 |
| institution | Directory Open Access Journal |
| issn | 1664-0640 |
| language | English |
| last_indexed | 2024-12-12T20:56:59Z |
| publishDate | 2020-10-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Psychiatry |
| spelling | doaj.art-996e3f8390b74a73bc89880171746d452022-12-22T00:12:16ZengFrontiers Media S.A.Frontiers in Psychiatry1664-06402020-10-011110.3389/fpsyt.2020.552532552532Risk Stratification for Bipolar Disorder Using Polygenic Risk Scores Among Young High-Risk AdultsSilvia Biere0Thorsten M. Kranz1Silke Matura2Kristiyana Petrova3Fabian Streit4Andreas G. Chiocchetti5Oliver Grimm6Murielle Brum7Natalie Brunkhorst-Kanaan8Viola Oertel9Aliaksandr Malyshau10Andrea Pfennig11Michael Bauer12Thomas G. Schulze13Sarah Kittel-Schneider14Sarah Kittel-Schneider15Andreas Reif16Department of Psychiatry, Psychosomatic Medicine and Psychotherapy, University Hospital, Goethe University, Frankfurt, GermanyDepartment of Psychiatry, Psychosomatic Medicine and Psychotherapy, University Hospital, Goethe University, Frankfurt, GermanyDepartment of Psychiatry, Psychosomatic Medicine and Psychotherapy, University Hospital, Goethe University, Frankfurt, GermanyDepartment of Psychiatry, Psychosomatic Medicine and Psychotherapy, University Hospital, Goethe University, Frankfurt, GermanyDepartment of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim/University of Heidelberg, Mannheim, GermanyDepartment of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, Autism Research and Intervention Center of Excellence Frankfurt, University Hospital Frankfurt, Goethe University, Frankfurt am Main, GermanyDepartment of Psychiatry, Psychosomatic Medicine and Psychotherapy, University Hospital, Goethe University, Frankfurt, GermanyDepartment of Psychiatry, Psychosomatic Medicine and Psychotherapy, University Hospital, Goethe University, Frankfurt, GermanyDepartment of Psychiatry, Psychosomatic Medicine and Psychotherapy, University Hospital, Goethe University, Frankfurt, GermanyDepartment of Psychiatry, Psychosomatic Medicine and Psychotherapy, University Hospital, Goethe University, Frankfurt, GermanyDepartment of Psychiatry, Psychosomatic Medicine and Psychotherapy, University Hospital, Goethe University, Frankfurt, GermanyDepartment of Psychiatry and Psychotherapy, Carl Gustav Carus University Hospital, Dresden University of Technology, Dresden, GermanyDepartment of Psychiatry and Psychotherapy, Carl Gustav Carus University Hospital, Dresden University of Technology, Dresden, GermanyInstitute of Psychiatric Phenomics and Genomics, University Hospital Munich, Ludwig-Maximilians-University of Munich, Munich, GermanyDepartment of Psychiatry, Psychosomatic Medicine and Psychotherapy, University Hospital, Goethe University, Frankfurt, GermanyDepartment of Psychiatry, Psychosomatic Medicine and Psychotherapy, University Hospital of Würzburg, University of Würzburg, Würzburg, GermanyDepartment of Psychiatry, Psychosomatic Medicine and Psychotherapy, University Hospital, Goethe University, Frankfurt, GermanyObjective: Identifying high-risk groups with an increased genetic liability for bipolar disorder (BD) will provide insights into the etiology of BD and contribute to early detection of BD. We used the BD polygenic risk score (PRS) derived from BD genome-wide association studies (GWAS) to explore how such genetic risk manifests in young, high-risk adults. We postulated that BD-PRS would be associated with risk factors for BD.Methods: A final sample of 185 young, high-risk German adults (aged 18–35 years) were grouped into three risk groups and compared to a healthy control group (n = 1,100). The risk groups comprised 117 cases with attention deficit hyperactivity disorder (ADHD), 45 with major depressive disorder (MDD), and 23 help-seeking adults with early recognition symptoms [ER: positive family history for BD, (sub)threshold affective symptomatology and/or mood swings, sleeping disorder]. BD-PRS was computed for each participant. Logistic regression models (controlling for sex, age, and the first five ancestry principal components) were used to assess associations of BD-PRS and the high-risk phenotypes.Results: We observed an association between BD-PRS and combined risk group status (OR = 1.48, p < 0.001), ADHD diagnosis (OR = 1.32, p = 0.009), MDD diagnosis (OR = 1.96, p < 0.001), and ER group status (OR = 1.7, p = 0.025; not significant after correction for multiple testing) compared to healthy controls.Conclusions: In the present study, increased genetic risk for BD was a significant predictor for MDD and ADHD status, but not for ER. These findings support an underlying shared risk for both MDD and BD as well as ADHD and BD. Improving our understanding of the underlying genetic architecture of these phenotypes may aid in early identification and risk stratification.https://www.frontiersin.org/articles/10.3389/fpsyt.2020.552532/fullpolygenic risk scorebipolar disordergenetic phenotypesdepressionADHDearly recognition |
| spellingShingle | Silvia Biere Thorsten M. Kranz Silke Matura Kristiyana Petrova Fabian Streit Andreas G. Chiocchetti Oliver Grimm Murielle Brum Natalie Brunkhorst-Kanaan Viola Oertel Aliaksandr Malyshau Andrea Pfennig Michael Bauer Thomas G. Schulze Sarah Kittel-Schneider Sarah Kittel-Schneider Andreas Reif Risk Stratification for Bipolar Disorder Using Polygenic Risk Scores Among Young High-Risk Adults Frontiers in Psychiatry polygenic risk score bipolar disorder genetic phenotypes depression ADHD early recognition |
| title | Risk Stratification for Bipolar Disorder Using Polygenic Risk Scores Among Young High-Risk Adults |
| title_full | Risk Stratification for Bipolar Disorder Using Polygenic Risk Scores Among Young High-Risk Adults |
| title_fullStr | Risk Stratification for Bipolar Disorder Using Polygenic Risk Scores Among Young High-Risk Adults |
| title_full_unstemmed | Risk Stratification for Bipolar Disorder Using Polygenic Risk Scores Among Young High-Risk Adults |
| title_short | Risk Stratification for Bipolar Disorder Using Polygenic Risk Scores Among Young High-Risk Adults |
| title_sort | risk stratification for bipolar disorder using polygenic risk scores among young high risk adults |
| topic | polygenic risk score bipolar disorder genetic phenotypes depression ADHD early recognition |
| url | https://www.frontiersin.org/articles/10.3389/fpsyt.2020.552532/full |
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