| Title: | Genome-wide gene-environment interactions in neuroticism: an exploratory study across 25 environments |
| Journal: | Translational Psychiatry |
| Published: | 22 Mar 2021 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/33753719/ |
| DOI: | https://doi.org/10.1038/s41398-021-01288-9 |
| URL: | https://www.nature.com/articles/s41398-021-01288-9.pdf |
| Citations: | 26 (18 in last 2 years) as of 8 Aug 2024 |
Publication 5059
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Abstract
Gene-environment interactions (GxE) are often suggested to play an important role in the aetiology of psychiatric phenotypes, yet so far, only a handful of genome-wide environment interaction studies (GWEIS) of psychiatric phenotypes have been conducted. Representing the most comprehensive effort of its kind to date, we used data from the UK Biobank to perform a series of GWEIS for neuroticism across 25 broadly conceptualised environmental risk factors (trauma, social support, drug use, physical health). We investigated interactions on the level of SNPs, genes, and gene-sets, and computed interaction-based polygenic risk scores (PRS) to predict neuroticism in an independent sample subset (N = 10,000). We found that the predictive ability of the interaction-based PRSs did not significantly improve beyond that of a traditional PRS based on SNP main effects from GWAS, but detected one variant and two gene-sets showing significant interaction signal after correction for the number of analysed environments. This study illustrates the possibilities and limitations of a comprehensive GWEIS in currently available sample sizes.7 Keywords
- Gene-Environment Interaction
- Genetic Predisposition to Disease
- Genome-Wide Association Study
- Humans
- Multifactorial Inheritance
- Neuroticism
- Polymorphism, Single Nucleotide
4 Authors
- Josefin Werme
- Sophie van der Sluis
- Danielle Posthuma
- Christiaan A. de Leeuw
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