| Title: | Contributions of common and rare genetic variation to different measures of mood and anxiety disorder in the UK Biobank |
| Journal: | BJPsych Open |
| Published: | 9 May 2025 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/40341140/ |
| DOI: | https://doi.org/10.1192/bjo.2025.43 |
| URL: | ~Ehttps://www.cambridge.org/core/services/aop-cambridge-core/content/view/71FF0C5A535ED2BD9063DC7D745ED538/S2056472425000432a.pdf/div-class-title-contributions-of-common-and-rare-genetic-variation-to-different-measures-of-mood-and-anxiety-disorder-in-the-uk-biobank-div.pdf~ |
Publication 15366
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Abstract
BACKGROUND: Mood and anxiety disorders co-occur and share symptoms, treatments and genetic risk, but it is unclear whether combining them into a single phenotype would better capture genetic variation. The contribution of common genetic variation to these disorders has been investigated using a range of measures; however, the differences in their ability to capture variation remain unclear, while the impact of rare variation is mostly unexplored.</p>
AIMS: We aimed to explore the contributions of common genetic variation and copy number variations associated with risk of psychiatric morbidity (P-CNVs) to different measures of internalising disorders.</p>
METHOD: We investigated eight definitions of mood and anxiety disorder, and a combined internalising disorder, derived from self-report questionnaires, diagnostic assessments and electronic healthcare records (EHRs). Association of these definitions with polygenic risk scores (PRSs) of major depressive disorder and anxiety disorder, as well as presence of a P-CNV, was assessed.</p>
RESULTS: The effect sizes of both PRSs and P-CNVs were similar for mood and anxiety disorder. Compared to mood and anxiety disorder, internalising disorder resulted in higher prediction accuracy for PRSs, and increased significance of associations with P-CNVs for most definitions. Comparison across the eight definitions showed that PRSs had higher prediction accuracy and effect sizes for stricter definitions, whereas P-CNVs were more strongly associated with EHR- and self-report-based definitions.</p>
CONCLUSIONS: Future studies may benefit from using a combined internalising disorder phenotype, and may need to consider that different phenotype definitions may be more informative depending on whether common or rare variation is studied.</p>
13 Authors
- Ioanna K. Katzourou
- LINC Consortium
- Inês Barroso
- Lauren Benger
- Andrés Ingason
- Daniel Stow
- Ruby Tsang
- Megan Wood
- George Kirov
- James Walters
- Michael J. Owen
- Peter Holmans
- Marianne B. M. van den Bree
1 Application
| Application ID | Title |
|---|---|
| 79704 | Physical and mental health multimorbidity across the lifespan (LIfespaN multimorbidity research Collaborative: LINC). |
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