Glycoprotein acetyls and depression: Testing for directionality and potential causality using longitudinal data and Mendelian randomization analyses
Year: 2023
Type: article
Study design: Observational Study
Abstract: BACKGROUND: Inflammation is associated with depression, but causality remains unclear. We investigated potential causality and direction of effect between inflammation and depression. METHODS: Using data from the ALSPAC birth cohort (n = 4021; 42.18 % male), we used multivariable regression to investigate bidirectional longitudinal associations of GlycA and depression and depression symptoms, assessed at ages 18y and 24y. We used two-sample Mendelian randomization (MR) to investigate potential causality and directionality. Genetic variants for GlycA were obtained from UK Biobank (UKB) (N = 115,078); for depression from the Psychiatric Genomics Consortium and UKB (N = 500,199); and for depressive symptoms (N = 161,460) from the Social Science Genetic Association Consortium. In addition to the Inverse Variance Weighted method, we used sensitivity analyses to strengthen causal inference. We conducted multivariable MR adjusting for body mass index (BMI) due to known genetic correlation between inflammation, depression and BMI. RESULTS: In the cohort analysis, after adjusting for potential confounders we found no evidence of associations between GlycA and depression symptoms score or vice versa. We observed an association between GlycA and depression (OR = 1∙18, 95 % CI: 1∙03-1∙36). MR suggested no causal effect of GlycA on depression, but there was a causal effect of depression on GlycA (mean difference in GlycA = 0∙09; 95 % CI: 0∙03-0∙16), which was maintained in some, but not all, sensitivity analyses. LIMITATIONS: The GWAS sample overlap could incur bias. CONCLUSION: We found no consistent evidence for an effect of GlycA on depression. There was evidence that depression increases GlycA in the MR analysis, but this may be confounded/mediated by BMI.
Source: Journal of Affective Disorders
Language: English
Subfield: Biological Psychiatry
Field: Neuroscience
Domain: Life Sciences
Open Access status: hybrid
Estimated APC paid: $3,210
Awards: Understanding the role of fatty acids in the aetiology of cardiovascular disease using novel causal inference methods, Reproductive and cardio-metabolic health, DTP Bid Led by Cardiff University, G1684393010, G1793884970, ALSPAC: consolidation of a two generation cell line backed resource, for the study of the environment and genetic determinants of health and development from before birth to late puberty., Neurobiological pathways from trauma exposure to child mental health outcomes in a high adversity South African Birth Cohort, Psychosis Immune Mechanism Stratified Medicine Study (PIMS), G2786058305, The Avon Longitudinal Study of Parents and Children (ALSPAC): A multi-generation, longitudinal resource, The Avon Longitudinal Study of Parents and Children (ALSPAC): A multi- generation, longitudinal resource focusing on life course health and well- being., G3948973784, G3987754321, G4060572169, The Avon Longitudinal Study of Parents and Children: An international resource for population
genomics and lifecourse epidemiology. Core Programme Support 2011-2015 and Core programme support 2014-2019, Caregiver influences on child psychological adjustment following trauma; a longitudinal study of a high adversity South African population, G5189661712, G5260012927, UK Biobank (core renewal), G5607908600, Immunopsychiatry: Investigating the role of inflammation in depression and other psychiatric disorders, G6487373758, G6940952066, Inflammation and Immunity in Depression: from novel mechanisms towards therapeutics, G710448223, Excessive drinking and alcohol related harms in Adulthood: ALSPAC at 24, G7737178365, G7895989498, The Avon Longitudinal Study of Parents and Children (ALSPAC): A multi-generation, longitudinal resource focusing on life course health and well-being., G8124202573, G8502142660, MICA: Mental Health Data Pathfinder: University of Cambridge, Cambridgeshire & Peterborough NHS Foundation Trust, and Microsoft, Religious belief, health, and disease: a family perspective. II. The follow-up and analyses, G8789231540
OpenAlex ID: W4376891002