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| Mental disorders; Mental illness; hypercholesterolemia; Mendelian randomization; Metabolic disorder syndrome |
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| English keywords:mental disorders, mental illness, high cholesterol, Mendelian randomization, metabolic disorder syndrome |
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| Background Patients with mental disorders are prone to metabolic syndrome (MetS), including elevated diastolic or systolic blood pressure, elevated fasting blood glucose, hypercholesterolemia, and abdominal obesity. As an important component of MetS, the relationship between hypercholesterolemia and mental illness has been discussed and speculated in previous studies. The increasing prevalence of mental disorders and hypercholesterolemia and the large number of co-occurrences have gradually led to systematic studies on causal relationships and related mechanisms. However, there is currently a lack of support from genome-wide association studies on whether mental disorders themselves cause hypercholesterolemia. Objective This study used a two-sample Mendelian randomization (MR) method to explore the potential causal association between mental disorders and hypercholesterolemia, test the strength of the correlation, exclude other confounding factors, and prove the robustness of the results. Methods The summary data of genome-wide association studies (GWAS) were analyzed, and single nucleotide polymorphisms (SNPs) closely associated with exposure factors such as mental disorders were used as instrumental variables (IVs), with hypercholesterolemia as the outcome variable. Causal analysis was performed using inverse variance weighting (IVW), MR-Egger method and weighted median method (WME method), and the results were supplemented by simple mode method (SM) and weighted mode method (WM). The causal relationship between mental disorders and the risk of hypercholesterolemia was evaluated by odds ratio (OR). Results A total of 36 SNPs associated with mental disorders were included as IV. With IVW as the main conclusion, the results showed that there was a causal relationship between mental disorders and hypercholesterolemia. For every additional patient with mental disorder, the risk of hypercholesterolemia would increase by 6.70% (IVW: OR=1.067, 95%CI: 1.014-1.128, P=0.001). The results of other methods (MR-Egger method, WME method, SM method, WM method) were basically consistent with the results of IVW method. Further verification of this conclusion showed that the causal relationship between mental disorders and the risk of hypercholesterolemia was not affected by genetic polymorphism (P=0.299). Cochrans'Q statistic and MR-Egger method were used to calculate the heterogeneity in IVW method, and the results showed that there was no significant heterogeneity (P>0.05). Further verification of reverse causal association showed no obvious evidence to support that hypercholesterolemia can cause mental disorders (P>0.05). Conclusion There is a causal relationship between mental disorders and hypercholesterolemia, and the probability of patients with mental disorders suffering from hypercholesterolemia may be increased. |
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