Shared genetic loci between depression and cardiometabolic traits

• Published in: PLoS genetics Vol. 18; no. 5; p. e1010161
• Main Authors: Torgersen, Kristin, Rahman, Zillur, Bahrami, Shahram, Hindley, Guy Frederick Lanyon, Parker, Nadine, Frei, Oleksandr, Shadrin, Alexey, O'Connell, Kevin S, Tesli, Martin, Smeland, Olav B, Munkhaugen, John, Djurovic, Srdjan, Dammen, Toril, Andreassen, Ole A
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 13-05-2022; Public Library of Science (PLoS)
• Subjects: Biology and Life Sciences; Blood pressure; Body mass index; C-reactive protein; C-Reactive Protein - genetics; Cardiovascular diseases; Cardiovascular Diseases - genetics; Cardiovascular system; Cholesterol; Coronary artery; Coronary Artery Disease - genetics; Depression - genetics; Depression, Mental; Diabetes mellitus (non-insulin dependent); Diabetes Mellitus, Type 2 - genetics; Epidemiology; Ethics; Gene loci; Gene mapping; Genetic aspects; Genetic Loci; Genetic Predisposition to Disease; Genetic relationship; Genome-wide association studies; Genome-Wide Association Study; Health aspects; Heart diseases; Humans; Linolenic acid; Lipids; Medicine and Health Sciences; Mental depression; Metabolism; Molecular modelling; Phenotype; Phenotypes; Polygenic inheritance; Polymorphism, Single Nucleotide - genetics; Psychological aspects; Quantitative trait loci; Risk factors; Norway
• ISSN: 1553-7404; 1553-7390; 1553-7404
• DOI: 10.1371/journal.pgen.1010161

Epidemiological and clinical studies have found associations between depression and cardiovascular disease risk factors, and coronary artery disease patients with depression have worse prognosis. The genetic relationship between depression and these cardiovascular phenotypes is not known. We here investigated overlap at the genome-wide level and in individual loci between depression, coronary artery disease and cardiovascular risk factors. We used the bivariate causal mixture model (MiXeR) to quantify genome-wide polygenic overlap and the conditional/conjunctional false discovery rate (pleioFDR) method to identify shared loci, based on genome-wide association study summary statistics on depression (n = 450,619), coronary artery disease (n = 502,713) and nine cardiovascular risk factors (n = 204,402-776,078). Genetic loci were functionally annotated using FUnctional Mapping and Annotation (FUMA). Of 13.9K variants influencing depression, 9.5K (SD 1.0K) were shared with body-mass index. Of 4.4K variants influencing systolic blood pressure, 2K were shared with depression. ConjFDR identified 79 unique loci associated with depression and coronary artery disease or cardiovascular risk factors. Six genomic loci were associated jointly with depression and coronary artery disease, 69 with blood pressure, 49 with lipids, 9 with type 2 diabetes and 8 with c-reactive protein at conjFDR < 0.05. Loci associated with increased risk for depression were also associated with increased risk of coronary artery disease and higher total cholesterol, low-density lipoprotein and c-reactive protein levels, while there was a mixed pattern of effect direction for the other risk factors. Functional analyses of the shared loci implicated metabolism of alpha-linolenic acid pathway for type 2 diabetes. Our results showed polygenic overlap between depression, coronary artery disease and several cardiovascular risk factors and suggest molecular mechanisms underlying the association between depression and increased cardiovascular disease risk.