scholarly journals Causally Associations of Blood Lipids Levels with COVID-19 Risk: Mendelian Randomization Study

2020 ◽  
Author(s):  
Kun Zhang ◽  
Yan Guo ◽  
Zhuo-Xin Wang ◽  
Jing-Miao Ding ◽  
Shi Yao ◽  
...  
Keyword(s):  
Blood Lipids ◽  
Mendelian Randomization ◽  
Causal Effect ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Lipoprotein Cholesterol ◽  
Gene Set Analysis ◽  
P Value ◽  
Comorbid Condition ◽  
Gene Set

AbstractBackgroundCoronavirus disease 2019 (COVID-19) is a global pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2). It has been found that coronary artery disease (CAD) is a comorbid condition for COVID-19. As the risk factors of CAD, whether blood lipids levels are causally related to increasing susceptibility and severity of COVID-19 is still unknown.DesignWe performed two-sample Mendelian Randomization (MR) analyses to explore whether dyslipidemia, low density lipoprotein cholesterol (LDL-c), high density lipoprotein cholesterol (HDL-c), triglyceride (TG) and total cholesterol (TC) were causally related to COVID-19 risk and severity. The GWAS summary data of blood lipids involving in 188,578 individuals and dyslipidemia in a total of 53,991 individuals were used as exposures, respectively. Two COVID-19 GWASs including 1,221 infected patients and 1,610 severe patients defined as respiratory failure were employed as outcomes. Based on the MR estimates, we further carried out gene-based and gene-set analysis to explain the potential mechanism for causal effect.ResultsThe MR results showed that dyslipidemia was casually associated with the susceptibility of COVID-19 and induced 27% higher odds for COVID-19 infection (MR-IVW OR = 1.27, 95% CI: 1.08 to 1.49, p-value = 3.18 × 10−3). Moreover, the increasing level of blood TC will raise 14 % higher odds for the susceptibility of COVID-19 (MR-IVW OR = 1.14, 95% CI: 1.04 to 1.25, p-value = 5.07 × 10−3). Gene-based analysis identified that ABO gene was associated with TC and the gene-set analysis found that immune processes were involved in the risk effect of TC.ConclusionsWe obtained three conclusions: 1) Dyslipidemia is casually associated with the susceptibility of COVID-19; 2) TC is a risk factor for the susceptibility of COVID-19; 3) The different susceptibility of COVID-19 in specific blood group may be partly explained by the TC concentration in diverse ABO blood groups.

scholarly journals Causally Associations of Blood Lipids Levels with COVID-19 Risk:  Mendelian Randomization Study

2020 ◽  
Author(s):  
Kun Zhang ◽  
Yan Guo ◽  
Zhuoxin Wang ◽  
Jingmiao Ding ◽  
Shi Yao ◽  
...  
Keyword(s):  
Blood Lipids ◽  
Mendelian Randomization ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Lipoprotein Cholesterol ◽  
P Value ◽  
Comorbid Condition ◽  
Global Pandemic ◽  
Artery Disease ◽  
Summary Data

Abstract BackgroundCoronavirus disease 2019 (COVID-19) is a global pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2). It has been found that coronary artery disease (CAD) is a comorbid condition for COVID-19. As the risk factors of CAD, whether blood lipids levels are causally related to increasing susceptibility and severity of COVID-19 is still unknown.ObjectiveWe aim to measure the causal effects between blood lipids and COVID-19 using two-sample Mendelian Randomization (MR) methods.MethodsWe performed two-sample MR analyses to explore whether dyslipidemia, low density lipoprotein cholesterol (LDL-c), high density lipoprotein cholesterol (HDL-c), triglyceride (TG) and total cholesterol (TC) were causally related to COVID-19 risk and severity. The GWAS summary data of blood lipids involving in 312571 individuals and dyslipidemia in a total of 53991 individuals were used as exposures, respectively. Two COVID-19 GWASs including 1221 infected patients and 1610 severe patients defined as respiratory failure were employed as outcomes. ResultsThe MR results showed that dyslipidemia was casually associated with the susceptibility of COVID-19 and induced 27% higher odds for COVID-19 infection (MR-IVW OR = 1.27, 95% CI: 1.08 to 1.49, p-value = 3·18 × 10-3). For blood lipids, the increasing level of TC will raise 18 % higher odds for the susceptibility of COVID-19 (MR-IVW OR = 1.18, 95% CI: 1.06 to 1.31, p-value = 3.08 × 10-3). Based on MR estimates, we further carried out gene-based analysis and found that ABO gene was associated with TC.Conclusions Dyslipidemia is casually associated with the susceptibility of COVID-19 and the blood TC level is a risk factor for the susceptibility of COVID-19. In addition, the different susceptibility of COVID-19 in specific blood group may be partly explained by the TC concentration in diverse ABO blood groups.

scholarly journals Causal Associations Between Blood Lipids and COVID-19 Risk: A Two-Sample Mendelian Randomization Study

2021 ◽  
Author(s):  
Kun Zhang ◽  
Shan-Shan Dong ◽  
Yan Guo ◽  
Shi-Hao Tang ◽  
Hao Wu ◽  
...  
Keyword(s):  
Total Cholesterol ◽  
Blood Lipids ◽  
Mendelian Randomization ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Outcome Data ◽  
Causal Effects ◽  
Lipoprotein Cholesterol ◽  
Global Pandemic ◽  
The Uk

Objective: Coronavirus disease 2019 (COVID-19) is a global pandemic caused by the severe acute respiratory syndrome coronavirus 2. It has been reported that dyslipidemia is correlated with COVID-19, and blood lipids levels, including total cholesterol, HDL-C (high-density lipoprotein cholesterol), and LDL-C (low-density lipoprotein cholesterol) levels, were significantly associated with disease severity. However, the causalities of blood lipids on COVID-19 are not clear. Approach and Results: We performed 2-sample Mendelian randomization (MR) analyses to explore the causal effects of blood lipids on COVID-19 susceptibility and severity. Using the outcome data from the UK Biobank (1221 cases and 4117 controls), we observed potential positive causal effects of dyslipidemia (odds ratio [OR], 1.27 [95% CI, 1.08–1.49], P =3.18×10 −3 ), total cholesterol (OR, 1.19 [95% CI, 1.07–1.32], P =8.54×10 −4 ), and ApoB (apolipoprotein B; OR, 1.18 [95% CI, 1.07–1.29], P =1.01×10 −3 ) on COVID-19 susceptibility after Bonferroni correction. In addition, the effects of total cholesterol (OR, 1.01 [95% CI, 1.00–1.02], P =2.29×10 −2 ) and ApoB (OR, 1.01 [95% CI, 1.00–1.02], P =2.22×10 −2 ) on COVID-19 susceptibility were also identified using outcome data from the host genetics initiative (14 134 cases and 1 284 876 controls). Conclusions: In conclusion, we found that higher total cholesterol and ApoB levels might increase the risk of COVID-19 infection.

scholarly journals Association between genetically determined leptin and blood lipids considering alcohol consumption: a Mendelian randomisation study

BMJ Open ◽  
2019 ◽  
Vol 9 (11) ◽  
pp. e026860 ◽  
Author(s):  
Luqi Shen ◽  
José F Cordero ◽  
Jia-Sheng Wang ◽  
Ye Shen ◽  
Shengxu Li ◽  
...  
Keyword(s):  
Alcohol Consumption ◽  
Alcohol Drinking ◽  
Blood Lipids ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Lipoprotein Cholesterol ◽  
Risk Scores ◽  
Mendelian Randomisation ◽  
Lipid Levels ◽  
Genetically Determined

ObjectivesThe objective of this study was to evaluate the association of genetically determined leptin with lipids.DesignWe conducted a Mendelian randomisation study to assess a potential causal relationship between serum leptin and lipid levels. We also evaluated whether alcohol drinking modified the associations of genetically determined leptin with blood lipids.Setting and participants3860 participants of the Framingham Heart Study third generation cohort.ResultsBoth genetic risk scores (GRSs), the GRS generated using leptin loci independent of body mass index (BMI) and GRS generated using leptin loci dependent of BMI, were positively associated with log-transformed leptin (log-leptin). The BMI-independent leptin GRS was associated with log-transformed triglycerides (log-TG, β=−0.66, p=0.01), but not low-density lipoprotein cholesterol (LDL-C, p=0.99), high-density lipoprotein cholesterol (HDL-C, p=0.44) or total cholesterol (TC, p=0.49). Instrumental variable estimation showed that per unit increase in genetically determined log-leptin was associated with 0.55 (95% CI: 0.05 to 1.00) units decrease in log-TG. Besides significant association with log-TG (β=−0.59, p=0.009), the BMI-dependent GRS was nominally associated with HDL-C (β=−10.67, p=0.09) and TC (β=−28.05, p=0.08). When stratified by drinking status, the BMI-dependent GRS was associated with reduced levels of LDL-C (p=0.03), log-TG (p=0.004) and TC (p=0.003) among non-current drinkers only. Significant interactions between the BMI-dependent GRS and alcohol drinking were identified for LDL-C (p=0.03), log-TG (p=0.03) and TC (p=0.02).ConclusionThese findings together indicated that genetically determined leptin was negatively associated with lipid levels and the association may be modified by alcohol consumption.

scholarly journals Study of gallbladder lesions and its relationship with serum lipid profile

2018 ◽  
Vol 5 (5) ◽  
pp. 1245
Author(s):  
Sushama Bhatta ◽  
Samir Singh
Keyword(s):  
Lipid Profile ◽  
Serum Lipid ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Chronic Cholecystitis ◽  
Lipoprotein Cholesterol ◽  
Serum Lipid Profile ◽  
P Value ◽  
Low Density Lipoprotein Cholesterol ◽  
Histopathological Lesion

Background: Gallbladder disease is one of the most common gastrointestinal diseases. Various studies have shown association between gallstone and alteration in serum lipids. The objective of this study was to evaluate histological patterns of cholecystectomy specimens and compare serum lipid profile of gallstone patients with controls.Methods: This study was conducted over a period of two years (April 2016 to April 2018). Records of 287 specimens who underwent cholecystectomy were analysed in which gallstones were found only in 186 patients. Out of 186 patients with gallstones, records of serum lipid profile were available in 32 patients which were compared with 32 control of similar age. Independent t- test was used to compare the data between cases and control.Results: Out of 287 cases, 68 were male and 219 were female with male to female ratio of 1:3.2. The predominant histopathological lesion was chronic cholecystitis (73.17%). Malignancy was observed in 0.7% cases. Serum total cholesterol, triglycerides and low density lipoprotein cholesterol were found to be higher and statistically significant in patients with gallstone compared to controls (p value 0.024, <0.001and 0.016 respectively). Serum High density lipoprotein cholesterol was lower in gallstone patient than in control but not statistically significant (p value 0.23).Conclusions: Chronic cholecystitis was the most common histopathological lesion. Serum total cholesterol, triglyceride and low density lipoprotein cholesterol level were elevated and statistically significant in patients with gallstone.

scholarly journals Mendelian randomization analysis rules out disylipidaemia as colorectal cancer cause

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Gemma Ibáñez-Sanz ◽  
Anna Díez-Villanueva ◽  
Marina Riera-Ponsati ◽  
Tania Fernández-Villa ◽  
Pablo Fernández Navarro ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Protective Factor ◽  
Mendelian Randomization ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Lipoprotein Cholesterol ◽  
Risk Scores ◽  
Lipid Levels ◽  
Risk Alleles ◽  
Statin Use

Abstract Dyslipidemia and statin use have been associated with colorectal cancer (CRC), but prospective studies have shown mixed results. We aimed to determine whether dyslipidemia is causally linked to CRC risk using a Mendelian randomization approach and to explore the association of statins with CRC. A case-control study was performed including 1336 CRC cases and 2744 controls (MCC-Spain). Subjects were administered an epidemiological questionnaire and were genotyped with an array which included polymorphisms associated with blood lipids levels, selected to avoid pleiotropy. Four genetic lipid scores specific for triglycerides (TG), high density lipoprotein cholesterol (HDL), low density lipoprotein cholesterol (LDL), or total cholesterol (TC) were created as the count of risk alleles. The genetic lipid scores were not associated with CRC. The ORs per 10 risk alleles, were for TG 0.91 (95%CI: 0.72–1.16, p = 0.44), for HDL 1.14 (95%CI: 0.95–1.37, p = 0.16), for LDL 0.97 (95%CI: 0.81–1.16, p = 0.73), and for TC 0.98 (95%CI: 0.84–1.17, p = 0.88). The LDL and TC genetic risk scores were associated with statin use, but not the HDL or TG. Statin use, overall, was a non-significant protective factor for CRC (OR 0.84; 95%CI: 0.70–1.01, p = 0.060), but lipophilic statins were associated with a CRC risk reduction (OR 0.78; 95%CI 0.66–0.96, p = 0.018). Using the Mendelian randomization approach, our study does not support the hypothesis that lipid levels are associated with the risk of CRC. This study does not rule out, however, a possible protective effect of statins in CRC by a mechanism unrelated to lipid levels.

scholarly journals Using a two-sample Mendelian randomization design to investigate a possible causal effect of maternal lipid concentrations on offspring birth weight

2019 ◽  
Vol 48 (5) ◽  
pp. 1457-1467 ◽  
Author(s):  
Liang-Dar Hwang ◽  
Deborah A Lawlor ◽  
Rachel M Freathy ◽  
David M Evans ◽  
Nicole M Warrington
Keyword(s):  
Birth Weight ◽  
Standard Deviation ◽  
Structural Equation ◽  
Genome Wide Association Study ◽  
Mendelian Randomization ◽  
Causal Effect ◽  
Density Lipoprotein ◽  
Lipoprotein Cholesterol ◽  
European Ancestry ◽  
The Impact

Abstract Background The intrauterine environment is critical for fetal growth and development. However, observational associations between maternal gestational lipid concentrations and offspring birth weight (BW) have been inconsistent and ascertaining causality is challenging. Methods We used a novel two-sample Mendelian randomization (MR) approach to estimate the causal effect of maternal gestational high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C) and triglyceride concentrations on offspring BW. Single nucleotide polymorphisms (SNPs) associated with serum HDL-C, LDL-C and triglyceride concentrations identified in the Global Lipids Genetics Consortium genome-wide association study meta-analysis (n = 188 577 European-ancestry individuals; sample 1) were selected as instrumental variables. The effects of these SNPs on offspring BW were estimated using a structural equation model in the UK Biobank and Early Growth Genetics consortium (n = 230 069 European-ancestry individuals; sample 2) that enabled partitioning of the genetic associations into maternal- (intrauterine) and fetal-specific effects. Results We found no evidence for a causal effect of maternal gestational HDL-C, LDL-C or triglyceride concentrations on offspring BW [standard deviation change in BW per standard deviation higher in HDL-C = −0.005 (95% confidence interval: −0.039, 0.029), LDL-C = 0.014 (−0.017, 0.045), and triglycerides = 0.014 (−0.025, 0.052)]. Conclusions Our findings suggest that maternal gestational HDL-C, LDL-C and triglyceride concentrations play a limited role in determining offspring BW. However, we cannot comment on the impact of these and other lipid fractions on fetal development more generally. Our study illustrates the power and flexibility of two-sample MR in assessing the causal effect of maternal environmental exposures on offspring outcomes.

scholarly journals A novel Mendelian randomization method identifies causal relationships between gene expression and low-density lipoprotein cholesterol levels

2019 ◽  
Author(s):  
Adriaan van der Graaf ◽  
Annique Claringbould ◽  
Antoine Rimbert ◽  
Harm-Jan Westra ◽  
Yang Li ◽  
...  
Keyword(s):  
Gene Expression ◽  
Complex Traits ◽  
Mendelian Randomization ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Lipoprotein Cholesterol ◽  
Low Density ◽  
Causal Relationships ◽  
Low Density Lipoprotein Cholesterol ◽  
Individual Level

AbstractRobust inference of causal relationships between gene expression and complex traits using Mendelian Randomization (MR) approaches is confounded by pleiotropy and linkage disequilibrium (LD) between gene expression quantitative loci (eQTLs). Here we propose a new MR method, MR-link, that accounts for unobserved pleiotropy and LD by leveraging information from individual-level data. In simulations, MR-link shows false positive rates close to expectation (median 0.05) and high power (up to 0.89), outperforming all other MR methods we tested, even when only one eQTL variant is present. Application of MR-link to low-density lipoprotein cholesterol (LDL-C) measurements in 12,449 individuals and eQTLs summary statistics from whole blood and liver identified 19 genes causally linked to LDL-C. These include the previously functionally validatedSORT1gene, and thePVRL2gene, located in theAPOElocus, for which a causal role in liver was yet unknown. Our results showcase the strength of MR-link for transcriptome-wide causal inferences.

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