| Title: | Depression with atypical neurovegetative symptoms shares genetic predisposition with immuno-metabolic traits and alcohol consumption |
| Journal: | Psychological Medicine |
| Published: | 6 Jul 2020 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/32624019/ |
| DOI: | https://doi.org/10.1017/s0033291720002342 |
| URL: | ~Ehttps://www.cambridge.org/core/services/aop-cambridge-core/content/view/1CEB0F0450730158C53A8E55C18F9EE6/S0033291720002342a.pdf/div-class-title-depression-with-atypical-neurovegetative-symptoms-shares-genetic-predisposition-with-immuno-metabolic-traits-and-alcohol-consumption-div.pdf~ |
Publication 2462
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Abstract
BACKGROUND: Depression is a highly prevalent and heterogeneous disorder. This study aims to determine whether depression with atypical features shows different heritability and different degree of overlap with polygenic risk for psychiatric and immuno-metabolic traits than other depression subgroups.</p>
METHODS: Data included 30 069 European ancestry individuals from the UK Biobank who met criteria for lifetime major depression. Participants reporting both weight gain and hypersomnia were classified as ↑WS depression (N = 1854) and the others as non-↑WS depression (N = 28 215). Cases with non-↑WS depression were further classified as ↓WS depression (i.e. weight loss and insomnia; N = 10 142). Polygenic risk scores (PRS) for 22 traits were generated using genome-wide summary statistics (Bonferroni corrected p = 2.1 × 10-4). Single-nucleotide polymorphism (SNP)-based heritability of depression subgroups was estimated.</p>
RESULTS: ↑WS depression had a higher polygenic risk for BMI [OR = 1.20 (1.15-1.26), p = 2.37 × 10-14] and C-reactive protein [OR = 1.11 (1.06-1.17), p = 8.86 × 10-06] v. non-↑WS depression and ↓WS depression. Leptin PRS was close to the significance threshold (p = 2.99 × 10-04), but the effect disappeared when considering GWAS summary statistics of leptin adjusted for BMI. PRS for daily alcohol use was inversely associated with ↑WS depression [OR = 0.88 (0.83-0.93), p = 1.04 × 10-05] v. non-↑WS depression. SNP-based heritability was not significantly different between ↑WS depression and ↓WS depression (14.3% and 12.2%, respectively).</p>
CONCLUSIONS: ↑WS depression shows evidence of distinct genetic predisposition to immune-metabolic traits and alcohol consumption. These genetic signals suggest that biological targets including immune-cardio-metabolic pathways may be relevant to therapies in individuals with ↑WS depression.</p>
9 Keywords
- Alcohol Drinking
- Depression
- Depressive Disorder, Major
- Genetic Predisposition to Disease
- Genome-Wide Association Study
- Humans
- Leptin
- Multifactorial Inheritance
- Polymorphism, Single Nucleotide
7 Authors
- Isabella Badini
- Jonathan R.I. Coleman
- Saskia P. Hagenaars
- Matthew Hotopf
- Gerome Breen
- Cathryn M. Lewis
- Chiara Fabbri
1 Application
| Application ID | Title |
|---|---|
| 18177 | Multi-trait GWAS analyses in the UK Biobank |
Enabling scientific discoveries that improve human health