| Title: | Multivariate genetic analysis of personality and cognitive traits reveals abundant pleiotropy |
| Journal: | Nature Human Behaviour |
| Published: | 26 Jun 2023 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/37365406/ |
| DOI: | https://doi.org/10.1038/s41562-023-01630-9 |
Publication 11594
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Abstract
Personality and cognitive function are heritable mental traits whose genetic foundations may be distributed across interconnected brain functions. Previous studies have typically treated these complex mental traits as distinct constructs. We applied the 'pleiotropy-informed' multivariate omnibus statistical test to genome-wide association studies of 35 measures of neuroticism and cognitive function from the UK Biobank (n = 336,993). We identified 431 significantly associated genetic loci with evidence of abundant shared genetic associations, across personality and cognitive function domains. Functional characterization implicated genes with significant tissue-specific expression in all tested brain tissues and brain-specific gene sets. We conditioned independent genome-wide association studies of the Big 5 personality traits and cognitive function on our multivariate findings, boosting genetic discovery in other personality traits and improving polygenic prediction. These findings advance our understanding of the polygenic architecture of these complex mental traits, indicating a prominence of pleiotropic genetic effects across higher order domains of mental function such as personality and cognitive function.</p>
23 Authors
- Guy Hindley
- Alexey A. Shadrin
- Dennis van der Meer
- Nadine Parker
- Weiqiu Cheng
- Kevin S. O'Connell
- Shahram Bahrami
- Aihua Lin
- Naz Karadag
- Børge Holen
- Thomas Bjella
- Ian J. Deary
- Gail Davies
- W. David Hill
- Jan Bressler
- Sudha Seshadri
- Chun Chieh Fan
- Torill Ueland
- Srdjan Djurovic
- Olav B. Smeland
- Oleksandr Frei
- Anders M. Dale
- Ole A. Andreassen
1 Application
| Application ID | Title |
|---|---|
| 27412 | Boosting the power of GWAS using novel statistical tools |
Enabling scientific discoveries that improve human health