scholarly journals Evaluation of bi-directional causal association between depression and cardiovascular diseases: a Mendelian randomization study

2020 ◽  
pp. 1-12
Author(s):  
Gloria Hoi-Yee Li ◽  
Ching-Lung Cheung ◽  
Albert Kar-Kin Chung ◽  
Bernard Man-Yung Cheung ◽  
Ian Chi-Kei Wong ◽  
...  
Keyword(s):  
Genetic Predisposition ◽  
Mendelian Randomization ◽  
Secondary Analysis ◽  
Blood Lipid ◽  
Genome Wide Association Studies ◽  
Causal Association ◽  
Lipid Levels ◽  
Increased Risk ◽  
Causal Pathway ◽  
Blood Lipid Levels

Abstract Background Depression and cardiovascular disease (CVD) are associated with each other but their relationship remains unclear. We aim to determine whether genetic predisposition to depression are causally linked to CVD [including coronary artery disease (CAD), myocardial infarction (MI), stroke and atrial fibrillation (AF)]. Methods Using summary statistics from the largest genome-wide association studies (GWAS) or GWAS meta-analysis of depression (primary analysis: n = 500 199), broad depression (help-seeking behavior for problems with nerves, anxiety, tension or depression; secondary analysis: n = 322 580), CAD (n = 184 305), MI (n = 171 875), stroke (n = 446 696) and AF (n = 1 030 836), genetic correlation was tested between two depression phenotypes and CVD [MI, stroke and AF (not CAD as its correlation was previously confirmed)]. Causality was inferred between correlated traits by Mendelian Randomization analyses. Results Both depression phenotypes were genetically correlated with MI (depression: rG = 0.169; p = 9.03 × 10−9; broad depression: rG = 0.123; p = 1 × 10−4) and AF (depression: rG = 0.112; p = 7.80 × 10−6; broad depression: rG = 0.126; p = 3.62 × 10−6). Genetically doubling the odds of depression was causally associated with increased risk of CAD (OR = 1.099; 95% CI 1.031–1.170; p = 0.004) and MI (OR = 1.146; 95% CI 1.070–1.228; p = 1.05 × 10−4). Adjustment for blood lipid levels/smoking status attenuated the causality between depression and CAD/MI. Null causal association was observed for CVD on depression. A similar pattern of results was observed in the secondary analysis for broad depression. Conclusions Genetic predisposition to depression may have positive causal roles on CAD/MI. Genetic susceptibility to self-awareness of mood problems may be a strong causal risk factor of CAD/MI. Blood lipid levels and smoking may potentially mediate the causal pathway. Prevention and early diagnosis of depression are important in the management of CAD/MI.

scholarly journals Association of 25 hydroxyvitamin D concentration with risk of COVID-19: a Mendelian randomization study

2020 ◽  
Author(s):  
Di Liu ◽  
Qiuyue Tian ◽  
Jie Zhang ◽  
Haifeng Hou ◽  
Wei Wang ◽  
...  
Keyword(s):  
Causal Relationship ◽  
Mendelian Randomization ◽  
Association Studies ◽  
Sensitivity Analyses ◽  
Genome Wide Association Studies ◽  
Causal Association ◽  
Hydroxyvitamin D ◽  
Increased Risk ◽  
25Ohd Concentration ◽  
25 Hydroxyvitamin D

Background In observational studies, 25 hydroxyvitamin D (25OHD) concentration has been associated with an increased risk of Coronavirus disease 2019 (COVID-19). However, it remains unclear whether this association is causal. Methods We performed a two-sample Mendelian randomization (MR) to explore the causal relationship between 25OHD concentration and COVID-19, using summary data from the genome-wide association studies (GWASs) and using 25OHD concentration-related SNPs as instrumental variables (IVs). Results MR analysis did not show any evidence of a causal association of 25OHD concentration with COVID-19 susceptibility and severity (odds ratio [OR]=1.136, 95% confidence interval [CI] 0.988-1.306, P=0.074; OR=0.889, 95% CI 0.549-1.439, P=0.632). Sensitivity analyses using different instruments and statistical models yielded similar findings, suggesting the robustness of the causal association. No obvious pleiotropy bias and heterogeneity were observed. Conclusion The MR analysis showed that there might be no linear causal relationship of 25OHD concentration with COVID-19 susceptibility and severity.

scholarly journals Causal Association of Trauma With Subsequent Psychiatric Disorder: A Mendelian Randomization Study

2021 ◽  
Author(s):  
Dongqing Gu ◽  
Shan Ou ◽  
Guodong Liu
Keyword(s):  
Psychiatric Disorder ◽  
Mood Disorder ◽  
Mendelian Randomization ◽  
Association Studies ◽  
Genome Wide Association Studies ◽  
Causal Association ◽  
Post Traumatic Stress ◽  
Mendelian Randomization Analysis ◽  
Increased Risk ◽  
Randomization Analysis

Abstract Objective Trauma has been proposed as a risk factor for the development of psychiatric disorder. This study aimed to determine the causal association between them. Methods Two-sample Mendelian randomization analyses were performed to estimate the causal association between trauma and psychiatric disorder. We obtained summary-level data for genetic variants associated with trauma and the corresponding association with psychiatric disorder from previous genome-wide association studies, and inverse variance weighted was used as the main method in our Mendelian randomization analysis. Results Genetically predisposed trauma was associated with an increased risk of psychiatric disorder (odds ratio [OR] = 1.02, 95% confidence interval [CI], 1.01–1.02,), mood disorder (OR = 1.01, 95% CI, 1.00-1.01) and depression (OR = 1.02, 95% CI, 1.01–1.02) in UK Biobank, as well as increased risk of mood disorder (OR = 1.23, 95% CI, 1.03–1.48), depression (OR = 1.10, 95% CI, 1.04–1.17), bipolar disorder (OR = 1.24, 95% CI, 1.04–1.49) and schizophrenia (OR = 1.47, 95% CI, 1.21–1.78) in data source from MR Base. However, Mendelian randomization evidence did not support an association between trauma and risk of post-traumatic stress disorder, anxiety disorder, sleep disorder, and eating disorder. Conclusions Findings from our Mendelian randomization analysis suggested that trauma might be causally associated with an increased risk of some common psychiatric disorder such as depression.

scholarly journals Association between maternal serum lipids during late pregnancy and adverse birth outcomes

2020 ◽  
Author(s):  
Meng-Yi Dai ◽  
Lu-Lin Wang ◽  
Yun-Tao Wu ◽  
Huan Li ◽  
Jian-Hong Xia ◽  
...  
Keyword(s):  
Birth Outcomes ◽  
Linear Trend ◽  
Late Pregnancy ◽  
Blood Lipid ◽  
Maternal Blood ◽  
Adverse Birth Outcomes ◽  
Lipid Levels ◽  
Increased Risk ◽  
Unit Increase ◽  
Blood Lipid Levels

Abstract Background: Adverse birth outcomes have short- and long-term impacts on maternal and child health. Maternal dyslipidemia during late pregnancy has been found to be associated with increased risk of adverse birth outcomes. However, similar evidence on association between maternal blood lipid levels and adverse birth outcomes is limited in China.Methods: The data were extracted from Guangdong Women and Children Hospital Information System from September 2014 to March 2018. A total of 3951 mother-newborn pairs were included in our study. Logistic regression model and linear trend analysis were conducted to analyze the correlation between maternal blood lipid levels and adverse birth outcomes after controlling potential confounders including gestational age, pre-pregnancy body mass index, fetal sex, and parity. Results: Among the 3951 subjects, the rates of macrosomia, large-for-gestational age (LGA), low birth weight infants (LBW), and preterm birth were 3.9% (154/3951), 8.5% (334/3951), 9.5% (377/3951), and 9.8% (388/3951), respectively. LDL was a risk factor for preterm birth (OR: 1.20; 95% CI: 1.08-1.34) while HDL was a protective factor (OR: 0.73; 95% CI: 0.55-0.96) after adjusting for covariates. As every unit increase in TG, the risk of macrosomia and LGA increased by 25% (adjusted OR: 1.25; 95% CI: 1.12-1.38) and 16% (adjusted OR: 1.16; 95% CI: 1.07-1.26), respectively. However, every unit increase in HDL concentration was associated with decreased risk for LGA (adjusted OR: 0.60; 95% CI: 0.44-0.81) and macrosomia (adjusted OR: 0.64; 95% CI: 0.41-0.99). High LDL concentrations were associated with a decreased risk of macrosomia (adjusted OR: 0.82; 95% CI: 0.68-0.99) and LGA (adjusted OR: 0.86; 95% CI: 0.76-0.98) but an increased risk of LBW (adjusted OR: 1.16; 95% CI: 1.04-1.30). The results of linear trend analysis were similar to those of logistic regression model.Conclusions: Maternal dyslipidemia during the third trimester is closely related to adverse birth outcomes. Monitoring and managing maternal blood lipid levels in an appropriate range may help to reduce the burden of adverse birth outcomes.

scholarly journals Network Mendelian randomization study: exploring the causal pathway from insomnia to type 2 diabetes

2022 ◽  
Vol 10 (1) ◽  
pp. e002510
Author(s):  
Wen Xiuyun ◽  
Lin Jiating ◽  
Xie Minjun ◽  
Li Weidong ◽  
Wu Qian ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Body Fat ◽  
Mendelian Randomization ◽  
Body Fat Percentage ◽  
Causal Association ◽  
Fat Percentage ◽  
Waist To Hip Ratio ◽  
Increased Risk ◽  
Causal Pathway

IntroductionInsomnia is a novel pathogen for type 2 diabetes mellitus (T2DM). However, mechanisms linking insomnia and T2DM are poorly understood. In this study, we apply a network Mendelian randomization (MR) framework to determine the causal association between insomnia and T2DM and identify the potential mediators, including overweight (body mass index (BMI), waist-to-hip ratio, and body fat percentage) and glycometabolism (HbA1c, fasting blood glucose, and fasting blood insulin).Research design and methodsWe use the MR framework to detect effect estimates of the insomnia–T2DM, insomnia–mediator, and mediator–T2DM associations. A mediator between insomnia and T2DM is established if MR studies in all 3 steps prove causal associations.ResultsIn the Inverse variance weighted method, the results show that insomnia will increase the T2DM risk (OR 1.142; 95% CI 1.072 to 1.216; p=0.000), without heterogeneity nor horizontal pleiotropy, strongly suggesting that genetically predicted insomnia has a causal association with T2DM. Besides, our MR analysis provides strong evidence that insomnia is causally associated with BMI and body fat percentage. There is also suggestive evidence of an association between insomnia and the waist-to-hip ratio. At the same time, our results indicate that insomnia is not causally associated with glycometabolism. Higher BMI, waist-to-hip ratio, and body fat percentage levels are strongly associated with increased risk of T2DM.ConclusionsGenetically predicted insomnia has a causal association with T2DM. Being overweight (especially BMI and body fat percentage) mediates the causal pathway from insomnia to T2DM.

Integrative analysis of scRNA-seq and GWAS data pinpoints periportal hepatocytes as the relevant liver cell types for blood lipids

2020 ◽  
Vol 29 (18) ◽  
pp. 3145-3153
Author(s):  
Xingjie Hao ◽  
Kai Wang ◽  
Chengguqiu Dai ◽  
Zeyang Ding ◽  
Wei Yang ◽  
...  
Keyword(s):  
Liver Cell ◽  
Blood Lipid ◽  
Cell Types ◽  
Specific Cell ◽  
Genome Wide Association Studies ◽  
Lipid Levels ◽  
Cell Type ◽  
Gene Sets ◽  
Human And Mouse ◽  
Blood Lipid Levels

Abstract Liver, a heterogeneous tissue consisting of various cell types, is known to be relevant for blood lipid traits. By integrating summary statistics from genome-wide association studies (GWAS) of lipid traits and single-cell transcriptome data of the liver, we sought to identify specific cell types in the liver that were most relevant for blood lipid levels. We conducted differential expression analyses for 40 cell types from human and mouse livers in order to construct the cell-type specifically expressed gene sets, which we refer to as construction of the liver cell-type specifically expressed gene sets (CT-SEGS). Under the assumption that CT-SEGS represented specific functions of each cell type, we applied stratified linkage disequilibrium score regression to determine cell types that were most relevant for complex traits and diseases. We first confirmed the validity of this method (of delineating functionally relevant cell types) by identifying the immune cell types as relevant for autoimmune diseases. We further showed that lipid GWAS signals were enriched in the human and mouse periportal hepatocytes. Our results provide important information to facilitate future cellular studies of the metabolic mechanism affecting blood lipid levels.

scholarly journals Association of 25 Hydroxyvitamin D Concentration with Risk of COVID-19: A Mendelian Randomization Study

2020 ◽  
Author(s):  
Di Liu ◽  
Qiuyue Tian ◽  
Jie Zhang ◽  
Haifeng Hou ◽  
Wei Wang ◽  
...  
Keyword(s):  
Causal Relationship ◽  
Mendelian Randomization ◽  
Association Studies ◽  
Sensitivity Analyses ◽  
Genome Wide Association Studies ◽  
Causal Association ◽  
Hydroxyvitamin D ◽  
Increased Risk ◽  
25Ohd Concentration ◽  
25 Hydroxyvitamin D

Abstract Background: Coronavirus disease 2019 (COVID-19) has caused a large global pandemic. In observational studies, 25 hydroxyvitamin D (25OHD) concentration has been associated with an increased risk of Coronavirus disease 2019 (COVID-19). However, it remains unclear whether this association is causal.Methods: We performed a two-sample Mendelian randomization (MR) to explore the causal relationship between 25OHD concentration and COVID-19, using summary data from the genome-wide association studies (GWASs) and using 25OHD concentration-related SNPs as instrumental variables (IVs). Results: MR analysis did not show any evidence of a causal association of 25OHD concentration with COVID-19 susceptibility and severity (odds ratio [OR]=1.136, 95% confidence interval [CI] 0.988-1.306, P=0.074; OR=0.889, 95% CI 0.549-1.439, P=0.632). Sensitivity analyses using different instruments and statistical models yielded similar findings, suggesting the robustness of the causal association. No obvious pleiotropy bias and heterogeneity were observed.Conclusions: The MR analysis showed that there might be no linear causal relationship of 25OHD concentration with COVID-19 susceptibility and severity.

Optimal blood lipid levels counterbalance high polygenic risk of coronary artery disease in 130 000 individuals

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
G Botta ◽  
A Bolli ◽  
P Di Domenico
Keyword(s):  
Genetic Risk ◽  
Significant Interaction ◽  
Blood Lipids ◽  
Blood Lipid ◽  
Lipid Levels ◽  
High Genetic Risk ◽  
Increased Risk ◽  
Artery Disease ◽  
Cad Risk ◽  
Blood Lipid Levels

Abstract Background Coronary artery disease (CAD) is a complex multifactorial disease leading cause of morbidity and mortality worldwide. Identifying individuals at high risk is crucial to guide life-style and therapeutics interventions. Polygenic Risk Score (PRS) is a weighted sum of common genetic variants that showed to be able to identify a population at greater than threefold risk of CAD compared to the average. Notably, individuals at high genetic risk who adhere to a healthy lifestyle displayed between two and three-fold relative risk reduction, compared to individuals with a poor lifestyle. Despite such evidences, a systematic assessment of the interplay between PRS and CAD risk factors such as blood lipid levels in contributing to the overall CAD risk is still lacking. Methods We analysed in more than 130.0000 individuals of the UK Biobank the association of incident CAD with PRS and blood lipids (LDL, TC, HDL, TC:HDL, LDL:HDL) using a Cox Proportional Hazard Model. We defined three populations: i) Carriers: PRS >95%, Reminders: PRS ≤95% and Reference: PRS ≤95% with optimal blood lipid levels. Carriers and Remainders were stratified by blood lipid levels according to international guidelines. We investigated a potential interaction between blood lipids and PRS and assessed the relative increased risk magnitude in Carriers and Reminders for different blood lipid levels. Results Carriers showed between two and three fold increased risk of incident CAD compared to Reminders at each non-optimal blood lipid level and their ratios. Carriers with LDL between 130 and 160 mg/dL showed higher CAD risk (HR 3.65, 95% CI 2.85–4.63) than Reminders with LDL above 190 mg/dL (HR 2.73, 95% CI 2.18–3.40). Despite that, Carriers displayed non significant increased risk respect to the Reference population for the following blood lipid thresholds: LDL <115 mg/dL, TC <200 mg/dL, HDL >70 mg/dL, LDL:HDL <2.0 and TC:HDL <3.5. The association between LDL cholesterol and CAD was modified by the PRS due to significant interaction (P-value <0.005). The magnitude of increased CAD risk by LDL was higher in Carriers (HR 1.64 95% CI 1.45–1.86 per LDL level) compared to Reminders (HR 1.40, 95% CI 1.34–1.46 per LDL level). Conclusion Using the largest prospective genotyped cohort available to date, we identified for the first time a significant interaction between LDL and genetics in determining CAD incidence. This result have deep implications in a CAD primary prevention perspective. For example individuals with high PRS and borderline-high LDL levels (130–159 mg/dL) are not currently considered to be at elevated risk, despite having higher CAD risk than Remainders with statin-recommended LDL level (>190 mg/dL). Finally, the evidence that optimal lipid levels counterbalance high genetic risk opens new scenarios in the research of targeted risk reduction in the era of precision medicine. Association between PRS and lipid levels Funding Acknowledgement Type of funding source: Public grant(s) – EU funding. Main funding source(s): EIT Health

scholarly journals Association between chronic periodontitis and serum lipid levels

2012 ◽  
Vol 69 (9) ◽  
pp. 771-777 ◽  
Author(s):  
Ana Pejcic ◽  
Ljiljana Kesic ◽  
Stevan Ilic ◽  
Zoran Pesic ◽  
Dimitrije Mirkovic
Keyword(s):  
Risk Factor ◽  
Periodontal Disease ◽  
Ldl Cholesterol ◽  
Density Lipoprotein ◽  
Blood Lipid ◽  
Lipoprotein Cholesterol ◽  
Lipid Levels ◽  
Periodontal Tissues ◽  
Increased Risk ◽  
Blood Lipid Levels

Background/Aim. Periodontitis is a local inflammatory process mediating destruction of periodontal tissues triggered by bacterial insult. However, this disease is also characterized by systemic inflammatory host responses that may contrbute, in part, to the recently reported increased risk for systemic diseases, including an altered lipid metabolism. On the other hand, many people in the world are affected by hyperlipidemia, which is a known risk faktor for atherosclerosis. The aim of this study was to determine the relationship between periodontal disease and blood lipid levels. Methods. A total of 50 patients with periodontitis included in this study had no documented history of recent acute coronary events. The healthy, non-periodontal subjects (comparison group) comprised 25 subjects. All the patients were periodontology examined and completed a medical history. Dental plaque index, probing depth, gingival index bleeding on probing and clinical attechment levels were recorded. Blood samples were taken on admission for measurements of serum total cholesterol, triglycerides, hight density lipoprotein cholesterol (HDL-cholesterol), and low density lipoprotein cholesterol (LDL-cholesterol). Results. The obtained results showed that mean levels of cholesterol (6.09 ? 1.61 mmol/L), triglycerdes (2.19+1.67mmol/l) and LDL cholesterol (4.09 ? 1.40 mmol/L) in individuals with periodontitis were higer, and levels od HDL (1.43 ? 0.51 mmol/L) was lower than those of individuals without periodontitis (4.86 ? 1.37; 1.14 ? 0.71; 3.18 ? 0.64; 1.53 ? 0.32 mmol/L, respectively). Conclusion. This study confirms a significant relationship between periodontal disease, regardless its intensity, and blood lipid levels in the studied population. The results imply that periodontitis may be a risk factor and may contribute to the pathogenesis of atherosclerosis and cardiovascular diseases (CVD). However, future prospective randomized studies have to determine whether periodontal disease is a risk factor for the occurrence of CVD.

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