| Title: | The influence of X chromosome variants on trait neuroticism |
| Journal: | Molecular Psychiatry |
| Published: | 6 Mar 2019 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/30842574/ |
| DOI: | https://doi.org/10.1038/s41380-019-0388-2 |
| URL: | https://www.nature.com/articles/s41380-019-0388-2.pdf |
| Citations: | 17 (5 in last 2 years) as of 8 Aug 2024 |
Publication 3185
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Abstract
Autosomal variants have successfully been associated with trait neuroticism in genome-wide analysis of adequately powered samples. But such studies have so far excluded the X chromosome from analysis. Here, we report genetic association analyses of X chromosome and XY pseudoautosomal single nucleotide polymorphisms (SNPs) and trait neuroticism using UK Biobank samples (N = 405,274). Significant association was found with neuroticism on the X chromosome for 204 markers found within three independent loci (a further 783 were suggestive). Most of the lead neuroticism-related X chromosome variants were located in intergenic regions (n = 397). Involvement of HS6ST2, which has been previously associated with sociability behaviour in the dog, was supported by single SNP and gene-based tests. We found that the amino acid and nucleotide sequences are highly conserved between dogs and humans. From the suggestive X chromosome variants, there were 19 nearby genes which could be linked to gene ontology information. Molecular function was primarily related to binding and catalytic activity; notable biological processes were cellular and metabolic, and nucleic acid binding and transcription factor protein classes were most commonly involved. X-variant heritability of neuroticism was estimated at 0.22% (SE = 0.05) from a full dosage compensation model. A polygenic X-variant score created in an independent sample (maximum N ≈ 7,300) did not predict significant variance in neuroticism, psychological distress, or depressive disorder. We conclude that the X chromosome harbours significant variants influencing neuroticism, and might prove important for other quantitative traits and complex disorders.</p>
10 Authors
- Michelle Luciano
- Gail Davies
- Kim M. Summers
- W. David Hill
- Caroline Hayward
- David C. Liewald
- David J. Porteous
- Catharine R. Gale
- Andrew M. McIntosh
- Ian J. Deary
1 Application
| Application ID | Title |
|---|---|
| 10279 | The relationship of cognitive function and negative emotions with morbidity and mortality: an aetiological investigation |
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