scholarly journals Estimating causal effects of atherogenic lipid-related traits on COVID-19 susceptibility and severity using a two-sample Mendelian randomization approach

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Masahiro Yoshikawa ◽  
Kensuke Asaba ◽  
Tomohiro Nakayama
Keyword(s):  
Risk Factors ◽  
Apolipoprotein B ◽  
Ldl Cholesterol ◽  
Mendelian Randomization ◽  
Serum Triglyceride ◽  
European Population ◽  
Causal Effects ◽  
Underlying Mechanisms ◽  
Mr Study ◽  
Atherogenic Lipid

Abstract Background As the number of COVID-19 deaths continues to rise worldwide, the identification of risk factors for the disease is an urgent issue, and it remains controversial whether atherogenic lipid-related traits including serum apolipoprotein B, low-density lipoprotein (LDL)-cholesterol, and triglyceride levels, are risk factors. The aim of this study was to estimate causal effects of lipid-related traits on COVID-19 risk in the European population using a two-sample Mendelian randomization (MR) approach. Methods We used summary statistics from a genome-wide association study (GWAS) that included 441,016 participants from the UK Biobank as the exposure dataset of lipid-related traits and from COVID-19 Host Genetics Initiative GWAS meta-analyses of European ancestry as the outcome dataset for COVID-19 susceptibility (32,494 cases and 1,316,207 controls), hospitalization (8316 cases and 1,549,095 controls), and severity (4792 cases and 1,054,664 controls). We performed two-sample MR analyses using the inverse variance weighted (IVW) method. As sensitivity analyses, the MR-Egger regression, weighted median, and weighted mode methods were conducted as were leave-one-out sensitivity analysis, the MR-PRESSO global test, PhenoScanner searches, and IVW multivariable MR analyses. A P value below 0.0055 with Bonferroni correction was considered statistically significant. Results This MR study suggested that serum apolipoprotein B or LDL-cholesterol levels were not significantly associated with COVID-19 risk. On the other hand, we inferred that higher serum triglyceride levels were suggestively associated with higher risks of COVID-19 susceptibility (odds ratio [OR] per standard deviation increase in lifelong triglyceride levels, 1.065; 95% confidence interval [CI], 1.001–1.13; P = 0.045) and hospitalization (OR, 1.174; 95% CI, 1.04–1.33; P = 0.012), and were significantly associated with COVID-19 severity (OR, 1.274; 95% CI, 1.08–1.50; P = 0.004). Sensitivity and bidirectional MR analyses suggested that horizontal pleiotropy and reverse causation were unlikely. Conclusions Our MR study indicates a causal effect of higher serum triglyceride levels on a greater risk of COVID-19 severity in the European population using the latest and largest GWAS datasets to date. However, as the underlying mechanisms remain unclear and our study might be still biased due to possible horizontal pleiotropy, further studies are warranted to validate our findings and investigate underlying mechanisms.

scholarly journals Particles and corrected particles of LDL and non-HDL are stronger predicters of coronary lesion in postmenopausal women

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Chuang Li ◽  
Jingxun Chen ◽  
Siyue Wei ◽  
Mei Zhang ◽  
Yushun Chu ◽  
...  
Keyword(s):  
Risk Factors ◽  
Postmenopausal Women ◽  
Apolipoprotein B ◽  
Operating Characteristic ◽  
Ldl Cholesterol ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Hdl Cholesterol ◽  
Spearman Correlation ◽  
Coronary Lesion

Abstract Background The optimum lipid indexes, predicting the coronary lesion in postmenopausal women are not clear. Objective To evaluate the optimum lipid predicter for coronary lesion in routine and advanced lipid tests. Method 300 postmenopausal women were enrolled and assigned into coronary heart disease (CHD) Group (242), and non-CHD Group (58). Routine and advanced lipid indexes were measured with standard laboratory test and nuclear magnetic resonance (NMR) spectroscopy. The correlation and predictivities for CHD of routine and advanced lipid indexes were performed with Logistic regression, Spearman correlation analysis and receiver operating characteristic (ROC). Results Age (hazard ratio (HR) 2.58, 95% confidence interval (CI) 1.08–5.86, P = 0.03), apolipoprotein B (ApoB) (HR 1.35, 95% CI 1.15–1.59, P < 0.001), corrected particles of low-density lipoprotein (LDL-p-corr) (HR 1.05, 95% CI 1.03–1.06, P < 0.001) and corrected particles of non-high-density lipoprotein (non-HDL-p-corr) (HR 1.02, 95% CI 1.01–1.03, P < 0.001) were the risk factors of CHD. LDL cholesterol (LDL-C), LDL-p, LDL-p-corr, HDL cholesterol (HDL-C), non-HDL cholesterol (non-HDL-C), non-HDL-p and non-HDL-p-corr were in linear correlation with Gensini score. Advanced lipid indexes LDL-p (area under curve (AUC) = 0.750, P = 0.02), LDL-p-corr (AUC = 0.759, P = 0.02), non-HDL-p (AUC = 0.693, P = 0.03) and non-HDL-p-corr (AUC = 0.699, P = 0.03) were more predictive for CHD than the routine ones (LDL-C and non-HDL-C). Conclusion In postmenopausal women, age, ApoB, LDL-p-corr and non-HDL-p-corr were risk factors of CHD. Compared with traditional lipid items, LDL-p, LDL-p-corr, non-HDL-p and non-HDL-p-corr may be better lipid indexes for CHD in postmenopausal women.

scholarly journals Causal Effect Between Total Cholesterol and HDL Cholesterol as Risk Factors for Chronic Kidney Disease: A Mendelian Randomization Study

2020 ◽  
Author(s):  
Liu Miao ◽  
Yan Min ◽  
Chuan-Meng Zhu ◽  
Jian-Hong Chen ◽  
Bin Qi ◽  
...  
Keyword(s):  
Total Cholesterol ◽  
Serum Lipid ◽  
Mendelian Randomization ◽  
Causal Effect ◽  
Hdl Cholesterol ◽  
Causal Effects ◽  
Lipid Levels ◽  
Serum Lipid Levels ◽  
Genome Wide ◽  
Mr Study

Abstract Background/Aims: While observational studies show an association between serum lipid levels and cardiovascular disease (CVD), intervention studies that examine the preventive effects of serum lipid levels on the development of CKD are lacking. Methods: To estimate the role of serum lipid levels in the etiology of CKD, we conducted a two-sample Mendelian randomization (MR) study on serum lipid levels. Single nucleotide polymorphisms (SNPs), which were significantly associated genome-wide with plasma serum lipid levels from the GLGC and CKDGen consortium genome-wide association study (GWAS), including total cholesterol (TC, n = 187365), triglyceride (TG, n = 177861), HDL cholesterol (HDL-C, n = 187167), LDL cholesterol (LDL-C, n = 173082), apolipoprotein A1 (ApoA1, n = 20687), apolipoprotein B (ApoB, n = 20690) and CKD (n = 117165), were used as instrumental variables. None of the lipid-related SNPs was associated with CKD (all P > 0.05). Results: MR analysis genetically predicted the causal effect between TC/HDL-C and CKD. The odds ratio (OR) and 95% confidence interval (CI) of TC within CKD was 0.756 (0.579 to 0.933) (P = 0.002), and HDL-C was 0.85 (0.687 to 1.012) (P = 0.049). No causal effects between TG, LDL-C- ApoA1, ApoB and CKD were observed. Sensitivity analyses confirmed that TC and HDL-C were significantly associated with CKD. Conclusions: The findings from this MR study indicate causal effects between TC, HDL-C and CKD. Decreased TC and elevated HDL-C may reduce the incidence of CKD but need to be further confirmed by using a genetic and environmental approach.

Heterozygous hypobetalipoproteinemia with fasting chylomicronemia

1991 ◽  
Vol 37 (2) ◽  
pp. 296-300
Author(s):  
G Huet ◽  
M C Dieu ◽  
A Martin ◽  
G Grard ◽  
J M Bard ◽  
...  
Keyword(s):  
Isoelectric Focusing ◽  
Apolipoprotein B ◽  
Ldl Cholesterol ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Serum Triglyceride ◽  
Low Density ◽  
Fasting Serum ◽  
Apolipoprotein C ◽  
Oral Fat Load

Abstract We describe a disorder in which low-density lipoprotein (LDL)-cholesterol and apolipoprotein B are in low concentration (0.47 mmol/L and 0.28 g/L, respectively) and chylomicrons are still present in plasma after an 18-h fast. The d less than 1.006 fraction was isolated by flotation ultracentrifugation and the apolipoproteins were analyzed by electrophoresis, immunoblotting with anti-apolipoprotein B-100 antiserum, and isoelectric focusing. In the d less than 1.006 fraction of the fasting serum, we found an apolipoprotein B form with the same apparent molecular mass as apolipoprotein B-48 and similar in amount to apolipoprotein B-100 (respective percentages, 46% and 54%). The monosialylated form of the apolipoprotein C-III was severely decreased. After an oral fat load, the repartition of the two species of apolipoprotein B did not change greatly (respective percentages, 60% and 40%), and the concentration of serum triglyceride increased only from 1.20 to 1.65 mmol/L.

scholarly journals Causal effects of cardiovascular risk factors on onset of major age-related diseases: A time-to-event Mendelian randomization study

2018 ◽  
Vol 107 ◽  
pp. 74-86 ◽  
Author(s):  
Liang He ◽  
Irina Culminskaya ◽  
Yury Loika ◽  
Konstantin G. Arbeev ◽  
Olivia Bagley ◽  
...  
Keyword(s):  
Risk Factors ◽  
Cardiovascular Risk ◽  
Cardiovascular Risk Factors ◽  
Mendelian Randomization ◽  
Causal Effects ◽  
Time To Event ◽  
Age Related

scholarly journals Increased pulse wave velocity strongly related to age in apparently healthy people of high cardiovascular risk population

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
G Zemtsovskaja ◽  
K Pilt ◽  
J Abina ◽  
K Meigas ◽  
M Viigimaa
Keyword(s):  
Risk Factors ◽  
Cardiovascular Risk ◽  
Arterial Stiffness ◽  
Pulse Wave Velocity ◽  
Apolipoprotein B ◽  
Ldl Cholesterol ◽  
Pulse Wave ◽  
Risk Level ◽  
Funding Source ◽  
Apparently Healthy

Abstract Introduction Pulse wave velocity (PWV) as a measure of arterial stiffness is associated with CVD morbidity and mortality. CVD mortality rates show Estonia (capital Tallinn) as being among high cardiovascular (CV) risk countries. Our study aimed to investigate the prevalence of increased PWV in Tallinn adults aged 20–65, apparently healthy (AH) at primary medical examination, and also to evaluate the association of increased PWV with age and biochemical cardiovascular risk factors at levels indicative of CV risk. Methods PWV measured by Arteriograph and biochemical CV risk factors by Cobas Roche 6000 analyzer were investigated in 805 responders of a cross-sectional population-based study of Tallinn adults aged 20–65, randomly selected from the Estonian Population Register by age decade and sex. Apparently healthy conditions were defined at primary visit as absence of hypertension (SBP &lt;140 and DBP &lt;90 mmHg), diabetes, obesity (BMI &lt;30 kg/m2), a history of known heart disease and medication usage against hyperlipidaemia. Statistical analysis was performed by MedCalc version 14.8.1. Results 445 people (men=180, women=265) were in AH conditions with median values (95% central range) of SBP, DBP, and BMI: 115 (94–137) mmHg, 73 (55–87) mmHg, and 24 (18–29) kg/m2. 27.4% of AH adults were smokers. Medians (95% central range) and indicative of CV risk level (with crude prevalence at this level) of other investigated CV risk factors were: PWV 6.2 (4.5–11.3), ≥9.7 m/s (24.7%); age 39 (23–62), ≥50 years (24.7%); total cholesterol 5.2 (3.7–7.2), &gt;5.0 mmol/L (57.1%); triglycerides 1.0 (0.5–2.7), ≥1.7 mmol/L (14.8%); apolipoprotein B 3.0 (1.7–4.7), &gt;2.6 /2.3 μmol/L for men/women (76.6%); HDL cholesterol 1.6 (1.0–2.6), &lt;1.0/1.3 mmol/L for men/women (7.0%); LDL cholesterol 3.2 (1.7–5.2), ≥3.0 mmol/L (82.7%); homocysteine 11.8 (7.1–20.2), ≥12.0 μmol/L (49%); lipoprotein (a) 0.1 (0.1–1.2), &gt;0.3 g/L (23.6%); high-sensitivity C-reactive protein 0.9 (0.2–6.8), &gt;3.0 mg/L (10.1%). Categorization of PWV values as indicative of CV risk (increased PWV) was made according to their interpretation by Arteriograph software as increased or abnormal. Stepwise logistic regression analysis of increased PWV along with age and biochemical risk factors revealed statistically significant and strong association only with age ≥50. Overall model fit p was &lt;0.0001, c-statistic 0.838, odds ratio 29.3. Conclusions Despite total cholesterol, apolipoprotein B, LDL cholesterol and homocysteine being at indicative of CV risk level in over 50% of AH people, increased PWV was observed only in about 6% of them. The study showed that being 50 years of age or older in a high risk population means 29 times greater probability of increased arterial stiffness than in younger ages, even without having hypertension, diabetes or obesity. This knowledge is important for preventive CVD strategy in this population group. Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): Estonian Ministry of Education and Research under institutional research financing

scholarly journals Investigating Causal Relations Between Circulating Metabolites and Alzheimer’s Diseases: A Mendelian Randomization Study

2021 ◽  
Author(s):  
Shu-Yi Huang ◽  
Yu-Xiang Yang ◽  
Ya-Ru Zhang ◽  
Kevin Kuo ◽  
Hong-Qi Li ◽  
...  
Keyword(s):  
Total Cholesterol ◽  
Ldl Cholesterol ◽  
Mendelian Randomization ◽  
Density Lipoprotein ◽  
Serum Total Cholesterol ◽  
Causal Effects ◽  
Sensitivity Analyses ◽  
Primary Analysis ◽  
Standard Deviation Increase ◽  
Increased Risk

Abstract BackgroundMetabolomics is a promising approach that can be used to understand pathophysiological pathways of Alzheimer disease (AD). However, the relationships between metabolism and AD are poorly understood. The aim of this study is to investigate the causal association between circulating metabolites and risk of AD by combining metabolomics with genomics through two-sample Mendelian randomization (MR) approach.MethodsGenetic associations with 123 circulating metabolic traits were utilized as exposures. A large summary statistics data from International Genomics of Alzheimer’s Project was used in primary analysis, including 21,982 AD cases and 41,944 controls. Validation was further performed using family history of AD data from UK Biobank (27,696 cases of maternal AD, 14,338 cases of paternal AD and 272,244 controls). We utilized the inverse-variance weighted method as primary analysis and four additional MR methods (MR-Egger, weighted median, weighted mode, and MR pleiotropy residual sum and outlier) for sensitivity analyses.ResultsWe found one-fold increased risk of developing AD per standard deviation increase in the levels of circulating ApoB (odd ratio (OR)=3.18; 95% confidence interval (CI): 1.52–6.66, P=0.0022) and glycoprotein acetyls (OR=1.21; 95% CI: 1.05–1.39, P=0.0093), serum total cholesterol (OR=2.73; 95% CI: 1.41-5.30, P=0.0030), and low-density lipoprotein (LDL) cholesterol (OR=2.34; 95% CI: 1.53-3.57, P=0.0001). Whereas glutamine (OR=0.81; 95% CI: 0.71-0.92, P=0.0011) were significantly associated with lower risk of AD. We also detected causal effects of several different composition of LDL fractions on increased AD risk, which has been verified in validation. However, we found no association between circulating high-density lipoprotein cholesterol and AD.ConclusionsOur findings provided robust evidence supporting causal effects of circulating glycoprotein acetyls, ApoB, LDL cholesterol, and serum total cholesterol on higher risk of AD, whereas glutamine showed the protective effect. Further research is required to decipher the biological pathways underpinning associations.

scholarly journals The Causal Effects of Health Conditions and Risk Factors on Social and Socioeconomic Outcomes: Mendelian Randomization in UK Biobank

2019 ◽  
Author(s):  
Sean Harrison ◽  
Alisha R Davies ◽  
Matt Dickson ◽  
Jessica Tyrrell ◽  
Michael J Green ◽  
...  
Keyword(s):  
Risk Factors ◽  
Household Income ◽  
Alcohol Intake ◽  
Mendelian Randomization ◽  
Causal Effects ◽  
Health Conditions ◽  
List Type ◽  
Uk Biobank ◽  
Socioeconomic Outcomes ◽  
University Degree

AbstractObjectivesTo estimate the causal effect of health conditions and risk factors on social and socioeconomic outcomes in UK Biobank. Evidence on socioeconomic impacts is important to understand because it can help governments, policy-makers and decision-makers allocate resources efficiently and effectively.DesignWe used Mendelian randomization to estimate the causal effects of eight health conditions (asthma, breast cancer, coronary heart disease, depression, eczema, migraine, osteoarthritis, type 2 diabetes) and five health risk factors (alcohol intake, body mass index [BMI], cholesterol, systolic blood pressure, smoking) on 19 social and socioeconomic outcomes.SettingUK Biobank.Participants337,009 men and women of white British ancestry, aged between 39 and 72 years.Main outcome measuresAnnual household income, employment, deprivation (measured by the Townsend deprivation index [TDI]), degree level education, happiness, loneliness, and 13 other social and socioeconomic outcomes.ResultsResults suggested that BMI, smoking and alcohol intake affect many socioeconomic outcomes. For example, smoking was estimated to reduce household income (mean difference = −£24,394, 95% confidence interval (CI): −£33,403 to −£15,384), the chance of owning accommodation (absolute percentage change [APC] = −21.5%, 95% CI: −29.3% to −13.6%), being satisfied with health (APC = −32.4%, 95% CI: −48.9% to −15.8%), and of obtaining a university degree (APC = −73.8%, 95% CI: −90.7% to −56.9%), while also increasing deprivation (mean difference in TDI = 1.89, 95% CI: 1.13 to 2.64, approximately 236% of a decile of TDI). There was evidence that asthma increased deprivation and decreased both household income and the chance of obtaining a university degree, and migraine reduced the chance of having a weekly leisure or social activity, especially in men. For other associations, estimates were null.ConclusionsHigher BMI, alcohol intake and smoking were all estimated to adversely affect multiple social and socioeconomic outcomes. Effects were not detected between health conditions and socioeconomic outcomes using Mendelian randomization, with the exceptions of depression, asthma and migraines. This may reflect true null associations, selection bias given the relative health and age of participants in UK Biobank, and/or lack of power to detect effects.What is known?Studies have shown associations between poor health and adverse social (e.g. wellbeing, social contact) and socioeconomic (e.g. educational attainment, income, employment) outcomes, but there is also strong evidence that social and socioeconomic factors influence health.These bidirectional relationships make it difficult to establish whether health conditions and health risk factors have causal effects on social and socioeconomic outcomes.Mendelian randomization is a technique that uses genetic variants robustly related to an exposure of interest (here, health conditions and risk factors for poor health) as a proxy for the exposure.Since genetic variants are randomly allocated at conception, they tend to be unrelated to the factors that typically confound observational studies, and are less likely to suffer from reverse causality, making causal inference from Mendelian randomization analyses more plausible.What this study addsThis study suggests causal effects of higher BMI, smoking and alcohol use on a range of social and socioeconomic outcomes, implying that population-level improvements in these risk factors may, in addition to the well-known health benefits, have social and socioeconomic benefits for individuals and society.There was evidence that asthma increased deprivation, decreased household income and the chance of having a university degree, migraine reduced the chance of having a weekly leisure or social activity, especially in men, and depression increased loneliness and decreased happiness.There was little evidence for causal effects of cholesterol, systolic blood pressure or breast cancer on social and socioeconomic outcomes.

scholarly journals Causal Effect Between Total Cholesterol and Hdl Cholesterol as Risk Factors for Chronic Kidney Disease: A Mendelian Randomization Study

2020 ◽  
Author(s):  
Liu Miao ◽  
Yan Min ◽  
Chuan-Meng Zhu ◽  
Jian-Hong Chen ◽  
Bin Qi ◽  
...  
Keyword(s):  
Total Cholesterol ◽  
Serum Lipid ◽  
Mendelian Randomization ◽  
Causal Effect ◽  
Hdl Cholesterol ◽  
Causal Effects ◽  
Lipid Levels ◽  
Serum Lipid Levels ◽  
Genome Wide ◽  
Mr Study

Abstract Background While observational studies show an association between serum lipid levels and cardiovascular disease (CVD), intervention studies that examine the preventive effects of serum lipid levels on the development of CKD are lacking. Methods To estimate the role of serum lipid levels in the etiology of CKD, we conducted a two-sample Mendelian randomization (MR) study on serum lipid levels. Single nucleotide polymorphisms (SNPs), which were significantly associated genome-wide with plasma serum lipid levels from the GLGC and CKDGen consortium genome-wide association study (GWAS), including total cholesterol (TC, n = 187365), triglyceride (TG, n = 177861), HDL cholesterol (HDL-C, n = 187167), LDL cholesterol (LDL-C, n = 173082), apolipoprotein A1 (ApoA1, n = 20687), apolipoprotein B (ApoB, n = 20690) and CKD (n = 117165), were used as instrumental variables. None of the lipid-related SNPs was associated with CKD (all P > 0.05). Results MR analysis genetically predicted the causal effect between TC/HDL-C and CKD. The odds ratio (OR) and 95% confidence interval (CI) of TC within CKD was 0.756 (0.579 to 0.933) (P = 0.002), and HDL-C was 0.85 (0.687 to 1.012) (P = 0.049). No causal effects between TG, LDL-C- ApoA1, ApoB and CKD were observed. Sensitivity analyses confirmed that TC and HDL-C were significantly associated with CKD. Conclusions The findings from this MR study indicate causal effects between TC, HDL-C and CKD. Decreased TC and elevated HDL-C may reduce the incidence of CKD but need to be further confirmed by using a genetic and environmental approach.

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