Badini, Isabella;
Coleman, Jonathan RI;
Hagenaars, Saskia P;
Hotopf, Matthew;
Breen, Gerome;
Lewis, Cathryn M;
Fabbri, Chiara;
(2022)
Depression with atypical neurovegetative symptoms shares genetic predisposition with immuno-metabolic traits and alcohol consumption.
Psychological Medicine
, 52
(4)
pp. 726-736.
10.1017/s0033291720002342.
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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. 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. 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). 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.
| Type: | Article |
|---|---|
| Title: | Depression with atypical neurovegetative symptoms shares genetic predisposition with immuno-metabolic traits and alcohol consumption |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1017/s0033291720002342 |
| Publisher version: | http://dx.doi.org/10.1017/s0033291720002342 |
| Language: | English |
| Additional information: | This is an Open Access article, distributed under the terms of the Creative Commons Attribution licence (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted re-use, distribution, and reproduction in any medium, provided the original work is properly cited. |
| Keywords: | Alcohol use, atypical depression, BMI, cardio-metabolic diseases, CRP, polygenic risk scores |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > Division of Psychiatry UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > Division of Psychiatry > Epidemiology and Applied Clinical Research |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10184163 |
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