Causal relationships between blood lipids and depression phenotypes: a Mendelian randomisation analysis. Issue 14 (24th October 2021)

• Record Type: Journal Article
• Authors: So, Hon-Cheong; Chau, Carlos Kwan-long; Cheng, Yu-ying; Sham, Pak C.
• Is Part Of: Psychological medicine. Volume 51:Issue 14(2021)
• Page Start: 2357
• Page End: 2369
• Publication Date: 2021-10-24
• Subjects: Causal inference -- depression -- genome-wide association study -- lipids -- Mendelian randomisation; Psychiatry -- Periodicals; Medicine and psychology -- Periodicals; Clinical psychology -- Periodicals; 616.89
• DOI: 10.1017/S0033291720000951
• Languages: English
• ISSNs: 0033-2917

Abstract

Abstract: Background: The etiology of depression remains poorly understood. Changes in blood lipid levels were reported to be associated with depression and suicide, however study findings were mixed. Methods: We performed a two-sample Mendelian randomisation (MR) analysis to investigate the causal relationship between blood lipids and depression phenotypes, based on large-scale GWAS summary statistics ( N = 188 577/480 359 for lipid/depression traits respectively). Five depression-related phenotypes were included, namely major depression (MD; from PGC), depressive symptoms (DS; from SSGAC), longest duration and number of episodes of low mood, and history of deliberate self-harm (DSH)/suicide (from UK Biobank). MR was conducted with inverse-variance weighted (MR-IVW), Egger and Generalised Summary-data-based MR (GSMR) methods. Results: There was consistent evidence that triglyceride (TG) is causally associated with DS (MR-IVW β for one-s.d. increase in TG = 0.0346, 95% CI 0.0114–0.0578), supported by MR-IVW and GSMR and multiple r 2 clumping thresholds. We also observed relatively consistent associations of TG with DSH/suicide (MR-Egger OR = 2.514, CI 1.579–4.003). There was moderate evidence for positive associations of TG with MD and the number of episodes of low mood. For HDL-c, we observed moderate evidence for causal associations with DS and MD. LDL-c and TC did not show robust causal relationships with depression phenotypes, except for weak evidence that LDL-c is inversely related to DSH/suicide. We did not detect significant associations when depression phenotypes were treated as exposures. Conclusions: This study provides evidence to a causal relationship between TG, and to a lesser extent, altered cholesterol levels with depression phenotypes. Further studies on its mechanistic basis and the effects of lipid-lowering therapies are warranted.