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

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.

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The effect of plasma lipids and lipid lowering interventions on bone mineral density: a Mendelian randomization study

10.1101/480426 ◽

2018 ◽

Cited By ~ 3

Author(s):

Jie Zheng ◽

Marie-Jo Brion ◽

John P. Kemp ◽

Nicole M. Warrington ◽

Maria-Carolina Borges ◽

...

Keyword(s):

Bone Mineral Density ◽

Standard Deviation ◽

Bone Mineral ◽

Mendelian Randomization ◽

Causal Effect ◽

Plasma Lipid ◽

Density Lipoprotein ◽

Lipid Lowering ◽

Lipid Levels ◽

Mineral Density

AbstractStatin treatment increases bone mineral density (BMD) and reduces fracture risk, but the underlying mechanism is unclear. We used Mendelian randomization (MR) to assess whether this relation is explained by a specific effect in response to statin use, or by a general effect of lipid-lowering. We utilized 400 single nucleotide polymorphisms (SNPs) robustly associated with plasma lipid levels and results from a heel BMD GWAS (derived from quantitative ultrasound) in 426,824 individuals from the UK Biobank. We performed univariate and multivariable MR analyses of low-density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C) and triglyceride levels on BMD. To test whether the effect of statins on BMD was mediated by lowering lipid levels, MR was repeated with and without SNPs in theHMGCRregion, the gene targeted by statins. Univariate MR analyses provided evidence for a causal effect of LDL-C on BMD (β= −0.060; −0.084 to −0.036; P = 4×10-6; standard deviation change in BMD per standard deviation change in LDL-C, with 95% CI), but not HDL or triglycerides. Multivariable MR analysis suggested that the effect of LDL-C on BMD was independent of HDL-C and triglycerides, and sensitivity analyses involving MR Egger and weighted median MR approaches suggested that the LDL-C results were robust to pleiotropy. MR analyses of LDL-C restricted to SNPs in theHMGCRregion showed similar effects on BMD(β= −0.083; −0.132 to −0.034; P = 0.001) to those excluding these SNPs (β= −0.063; −0.090 to −0.036; P = 8×10-6). Bidirectional MR analyses provided some evidence for a causal effect of BMD on plasma LDL-C levels. Our results suggest that effects of statins on BMD are at least partly due to their LDL-C lowering effect. Further studies are required to examine the potential role of modifying plasma lipid levels in treating osteoporosis.

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A multivariable Mendelian randomization analysis investigating smoking and alcohol consumption in oral and oropharyngeal cancer

Nature Communications ◽

10.1038/s41467-020-19822-6 ◽

2020 ◽

Vol 11 (1) ◽

Author(s):

Mark Gormley ◽

Tom Dudding ◽

Eleanor Sanderson ◽

Richard M. Martin ◽

Steven Thomas ◽

...

Keyword(s):

Standard Deviation ◽

Alcohol Consumption ◽

Oropharyngeal Cancer ◽

Genome Wide Association Study ◽

Mendelian Randomization ◽

Causal Effect ◽

Strong Association ◽

Smoking Behaviour ◽

Standard Deviation Increase ◽

Independent Effects

AbstractThe independent effects of smoking and alcohol in head and neck cancer are not clear, given the strong association between these risk factors. Their apparent synergistic effect reported in previous observational studies may also underestimate independent effects. Here we report multivariable Mendelian randomization performed in a two-sample approach using summary data on 6,034 oral/oropharyngeal cases and 6,585 controls from a recent genome-wide association study. Our results demonstrate strong evidence for an independent causal effect of smoking on oral/oropharyngeal cancer (IVW OR 2.6, 95% CI = 1.7, 3.9 per standard deviation increase in lifetime smoking behaviour) and an independent causal effect of alcohol consumption when controlling for smoking (IVW OR 2.1, 95% CI = 1.1, 3.8 per standard deviation increase in drinks consumed per week). This suggests the possibility that the causal effect of alcohol may have been underestimated. However, the extent to which alcohol is modified by smoking requires further investigation.

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Maternal polycystic ovary syndrome and offspring birth weight: a Mendelian randomization study

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/clinem/dgab843 ◽

2021 ◽

Author(s):

Yuexin Gan ◽

Donghao Lu ◽

Chonghuai Yan ◽

Jun Zhang ◽

Jian Zhao

Keyword(s):

Birth Weight ◽

Polycystic Ovary Syndrome ◽

Causal Relationship ◽

Mendelian Randomization ◽

Polycystic Ovary ◽

Causal Effect ◽

Sensitivity Analyses ◽

European Ancestry ◽

Ovary Syndrome ◽

Genetic Instruments

Abstract Background Observational associations between maternal polycystic ovary syndrome (PCOS) and offspring birth weight (BW) have been inconsistent and the causal relationship is still uncertain. Objective We conducted a two-sample Mendelian randomization (MR) study to estimate the causal effect of maternal PCOS on offspring BW. Methods We constructed genetic instruments for PCOS with 14 single nucleotide polymorphisms (SNPs) which were identified in the genome-wide association study (GWAS) meta-analysis including 10,074 PCOS cases and 103,164 controls of European ancestry from seven cohorts. The genetic associations of these SNPs with the offspring BW were extracted from summary statistics estimated by the Early Growth Genetics (EGG) consortium (n = 406,063 European-ancestry individuals) using the weighted linear model (WLM), an approximation method of structural equation model (SEM), which separated maternal genetic effects from fetal genetic effects. We used a two-sample MR design to examine the causal relationship between maternal PCOS and offspring BW. Sensitivity analyses were conducted to assess the robustness of the MR results. Results We found little evidence for a causal effect of maternal PCOS on offspring BW (-6.1 g, 95% confidence interval [CI]: -16.8 g, 4.6 g). Broadly consistent results were found in the sensitivity analyses. Conclusion Despite the large scale of this study, our results suggested little causal effect of maternal PCOS on offspring BW. MR studies with a larger sample size of women with PCOS or more genetic instruments that would increase the variation of PCOS explained are needed in the future.

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Metabolic Traits and Stroke Risk in Individuals of African Ancestry: Mendelian Randomization Analysis

Stroke ◽

10.1161/strokeaha.121.034747 ◽

2021 ◽

Author(s):

Segun Fatumo ◽

Ville Karhunen ◽

Tinashe Chikowore ◽

Toure Sounkou ◽

Brenda Udosen ◽

...

Keyword(s):

Total Cholesterol ◽

Genetic Association ◽

Mendelian Randomization ◽

African Ancestry ◽

Density Lipoprotein ◽

Lipoprotein Cholesterol ◽

European Ancestry ◽

Minority Population ◽

Genome Wide Association Studies ◽

Metabolic Traits

Background and Purpose: Metabolic traits affect ischemic stroke (IS) risk, but the degree to which this varies across different ethnic ancestries is not known. Our aim was to apply Mendelian randomization to investigate the causal effects of type 2 diabetes (T2D) liability and lipid traits on IS risk in African ancestry individuals, and to compare them to estimates obtained in European ancestry individuals. Methods: For African ancestry individuals, genetic proxies for T2D liability and circulating lipids were obtained from a meta-analysis of the African Partnership for Chronic Disease Research study, the UK Biobank, and the Million Veteran Program (total N=77 061). Genetic association estimates for IS risk were obtained from the Consortium of Minority Population Genome-Wide Association Studies of Stroke (3734 cases and 18 317 controls). For European ancestry individuals, genetic proxies for the same metabolic traits were obtained from Million Veteran Program (lipids N=297 626, T2D N=148 726 cases, and 965 732 controls), and genetic association estimates for IS risk were obtained from the MEGASTROKE study (34 217 cases and 406 111 controls). Random-effects inverse-variance weighted Mendelian randomization was used as the main method, complemented with sensitivity analyses more robust to pleiotropy. Results: Higher genetically proxied T2D liability, LDL-C (low-density lipoprotein cholesterol), total cholesterol and lower genetically proxied HDL-C (high-density lipoprotein cholesterol) were associated with increased risk of IS in African ancestry individuals (odds ratio per doubling the odds of T2D liability [95% CI], 1.09 [1.07–1.11]; per standard-deviation increase in LDL-C, 1.12 [1.04–1.21]; total cholesterol: 1.23 [1.06–1.43]; HDL-C, 0.93 [0.89–0.99]). There was no evidence for differences in these estimates when performing analyses in European ancestry individuals. Conclusions: Our analyses support a causal effect of T2D liability and lipid traits on IS risk in African ancestry individuals, with Mendelian randomization estimates similar to those obtained in European ancestry individuals.

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Association between birth weight and refractive error in adulthood: a Mendelian randomisation study

British Journal of Ophthalmology ◽

10.1136/bjophthalmol-2018-313640 ◽

2019 ◽

Vol 104 (2) ◽

pp. 214-219 ◽

Cited By ~ 3

Author(s):

Denis Plotnikov ◽

Cathy Williams ◽

Jeremy A Guggenheim

Keyword(s):

Birth Weight ◽

Refractive Error ◽

Genome Wide Association Study ◽

Causal Effect ◽

Ordinary Least Squares ◽

Mendelian Randomisation ◽

Uk Biobank ◽

Normal Range ◽

A Genome ◽

The Impact

BackgroundPathological myopia is one of the leading causes of blindness globally. Lower birth weight (BW) within the normal range has been reported to increase the risk of myopia, although findings conflict. We sought to estimate the causal effect of BW on refractive error using Mendelian randomisation (MR), under the assumption of a linear relationship.MethodsGenetic variants associated with BW were identified from meta-analysis of a genome-wide association study (GWAS) for self-reported BW in 162 039 UK Biobank participants and a published Early Growth Genetics (EGG) consortium GWAS (n=26 836). We performed a one-sample MR analysis in 39 658 unrelated, adult UK Biobank participants (independent of the GWAS sample) using an allele score for BW as instrumental variable. A two-sample MR sensitivity analysis and conventional ordinary least squares (OLS) regression analyses were also undertaken.ResultsIn OLS analysis, BW showed a small, positive association with refractive error: +0.04 D per SD increase in BW (95% CI 0.02 to 0.07; p=0.002). The one-sample MR-estimated causal effect of BW on refractive error was higher, at +0.28 D per SD increase in BW (95% CI 0.05 to 0.52, p=0.02). A two-sample MR analysis provided similar causal effect estimates, with minimal evidence of directional pleiotropy.ConclusionsOur study suggests lower BW within the normal range is causally associated with a more myopic refractive error. However, the impact of the causal effect was modest (range 1.00 D covering approximately 95% of the population).

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

10.1101/2020.07.07.20147926 ◽

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.

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Casual Effect of Serum Lipid Biomarkers On Early Age-Related Macular Degeneration Using Mendelian Randomization

10.21203/rs.3.rs-1018388/v1 ◽

2021 ◽

Author(s):

Fen-Fen Li ◽

Yuqin Wang ◽

Qi Chen ◽

Lue Xiang ◽

Feng-Qin Rao ◽

...

Keyword(s):

Macular Degeneration ◽

Serum Lipid ◽

Mendelian Randomization ◽

Density Lipoprotein ◽

Lipid Biomarkers ◽

Age Related Macular Degeneration ◽

Lipoprotein Cholesterol ◽

European Ancestry ◽

Age Related ◽

Increased Risk

Abstract Background Age-related macular degeneration (AMD) is one of the major causes of vision loss. Early AMD needs to be taken seriously, whereas lipid biomarkers’ casual effects on early AMD remain unclear. Methods In this study, a two-sample Mendelian randomization (MR) analysis was performed to systematically assess the causal relationships between seven serum lipid biomarkers, consisting of apolipoprotein A (ApoA), apolipoprotein B (ApoB), total cholesterol (CHOL), high-density lipoprotein cholesterol (HDL-C), direct low-density lipoprotein cholesterol (LDL-C), lipoprotein A [Lp(a)], and triglycerides (TG), and the risk of early AMD. Totally, 14,034 cases and 91,214 controls of European ancestry were included in the analysis (Number of SNPs = 11,304,110). Results MR estimates showed that a higher HDL-C level was strongly associated with increased risk of early AMD (OR = 1.25, 95% CI: 1.15-1.35, P = 2.61 × 10−8). In addition, the level of ApoA was also positively associated with the risk of early AMD (OR = 2.04, 95% CI: 1.50-2.77, P = 6.27 × 10−6). Conversely, higher LDL-C levels significantly decreased the risk of early AMD (OR = 0.90, 95% CI: 0.85-0.96, P = 2.03 × 10−3). In addition to LDL-C, higher levels of ApoB and TG were found to be positively associated with early AMD risk. Sensitivity analyses further supported these associations. Moreover, multivariable MR analyses, adjusting for the effects of correlated lipid biomarkers yielded similar results. Conclusion This study addresses the question of causality relationships that elevated circulating HDL-C/ApoA levels and increased risk of early AMD, whereas LDL-C, ApoB, and TG specifically reduce the risk of early AMD. These findings contribute to our better understanding of the role of lipid metabolism in drusen formation, particularly in early AMD development.

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Investigating causal relationships between exposome and human longevity: a Mendelian randomization analysis

BMC Medicine ◽

10.1186/s12916-021-02030-4 ◽

2021 ◽

Vol 19 (1) ◽

Author(s):

Shu-Yi Huang ◽

Yu-Xiang Yang ◽

Shi-Dong Chen ◽

Hong-Qi Li ◽

Xue-Qing Zhang ◽

...

Keyword(s):

Venous Thromboembolism ◽

Body Fat ◽

Mendelian Randomization ◽

Density Lipoprotein ◽

Environmental Exposures ◽

Lipoprotein Cholesterol ◽

European Ancestry ◽

Human Longevity ◽

Lower Odds ◽

Age Related

Abstract Background Environmental factors are associated with human longevity, but their specificity and causality remain mostly unclear. By integrating the innovative “exposome” concept developed in the field of environmental epidemiology, this study aims to determine the components of exposome causally linked to longevity using Mendelian randomization (MR) approach. Methods A total of 4587 environmental exposures extracting from 361,194 individuals from the UK biobank, in exogenous and endogenous domains of exposome were assessed. We examined the relationship between each environmental factor and two longevity outcomes (i.e., surviving to the 90th or 99th percentile age) from various cohorts of European ancestry. Significant results after false discovery rates correction underwent validation using an independent exposure dataset. Results Out of all the environmental exposures, eight age-related diseases and pathological conditions were causally associated with lower odds of longevity, including coronary atherosclerosis (odds ratio = 0.77, 95% confidence interval [0.70, 0.84], P = 4.2 × 10−8), ischemic heart disease (0.66, [0.51, 0.87], P = 0.0029), angina (0.73, [0.65, 0.83], P = 5.4 × 10−7), Alzheimer’s disease (0.80, [0.72, 0.89], P = 3.0 × 10−5), hypertension (0.70, [0.64, 0.77], P = 4.5 × 10−14), type 2 diabetes (0.88 [0.80, 0.96], P = 0.004), high cholesterol (0.81, [0.72, 0.91], P = 0.0003), and venous thromboembolism (0.92, [0.87, 0.97], P = 0.0028). After adjusting for genetic correlation between different types of blood lipids, higher levels of low-density lipoprotein cholesterol (0.72 [0.64, 0.80], P = 2.3 × 10−9) was associated with lower odds of longevity, while high-density lipoprotein cholesterol (1.36 [1.13, 1.62], P = 0.001) showed the opposite. Genetically predicted sitting/standing height was unrelated to longevity, while higher comparative height size at 10 was negatively associated with longevity. Greater body fat, especially the trunk fat mass, and never eat sugar or foods/drinks containing sugar were adversely associated with longevity, while education attainment showed the opposite. Conclusions The present study supports that some age-related diseases as well as education are causally related to longevity and highlights several new targets for achieving longevity, including management of venous thromboembolism, appropriate intake of sugar, and control of body fat. Our results warrant further studies to elucidate the underlying mechanisms of these reported causal associations.

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Using multiple Mendelian randomization approaches and genetic correlations to understand obesity, urate, and gout

Scientific Reports ◽

10.1038/s41598-021-97410-4 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Charleen D. Adams ◽

Brian B. Boutwell

Keyword(s):

Observational Studies ◽

Genome Wide Association Study ◽

Mendelian Randomization ◽

Low Density Lipoprotein ◽

Genetic Correlations ◽

Density Lipoprotein ◽

Lipoprotein Cholesterol ◽

Low Density Lipoprotein Cholesterol ◽

Genome Wide ◽

Genetically Determined

AbstractObservational studies suggest relationships between obesity, urate, and gout but are possibly confounded. We assessed whether genetically determined obesity, higher urate (and related traits), and gout were causal using multiple Mendelian randomization (MR) approaches and linkage disequilibrium score regression for genetic correlations (rg). For data, we used genome-wide association study summary statistics available through MR-Base. We observed that obesity increased urate (beta = 0.127; 95% CI = 0.098, 0.157; P-value = 1.2E−17; rg = 0.25 [P-value = 0.001]) and triglycerides (beta = 0.082; 95% CI = 0.065, 0.099; P-value = 1.2E−21; rg = 0.23 [P-value = 8.8E−12]) and decreased high-density lipoprotein cholesterol (HDL) (beta = − 0.083; 95% CI = − 0.101, − 0.065; P-value = 2.5E−19; rg = − 0.28; [P-value = 5.2E−24]). Higher triglycerides increased urate (beta = 0.198; 95% CI = 0.146, 0.251; P-value = 8.9E−14; rg = 0.29 [P-value = 0.001]) and higher HDL decreased urate (beta = − 0.109; 95% CI = − 0.148, − 0.071; P-value = 2.7E− 08; rg = − 0.21 [P-value = 9.8E−05]). Higher urate (OR = 1.030; 95% CI = 1.028, 1.032; P-value = 1.1E−130; rg = 0.89 [P-value = 1.7E−55]) and obesity caused gout (OR = 1.003; 95% CI = 1.001, 1.004; P-value = 1.3E−04; rg = 0.23 [P-value = 2.7E−05]). Obesity on gout with urate as a mediator revealed all the effect of obesity on gout occurred through urate. Obesity on low-density lipoprotein cholesterol (LDL) was null (beta = −0.011; 95% CI = −0.030, 0.008; P-value = 2.6E−01; rg = 0.03 [P-value = 0.369]). A multivariable MR of obesity, HDL, and triglycerides on urate showed obesity influenced urate when accounting for HDL and triglycerides. Obesity’s impact on urate was exacerbated by it decreasing HDL.

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The Relationship between Blood Lipids and Risk of Atrial Fibrillation: Univariable and Multivariable Mendelian Randomization Analysis

Nutrients ◽

10.3390/nu14010181 ◽

2021 ◽

Vol 14 (1) ◽

pp. 181

Author(s):

Shengyi Yang ◽

Rupak Pudasaini ◽

Hong Zhi ◽

Lina Wang

Keyword(s):

Atrial Fibrillation ◽

Apolipoprotein B ◽

Blood Lipids ◽

Mendelian Randomization ◽

Density Lipoprotein ◽

Genetic Evidence ◽

Apolipoprotein A1 ◽

Lipoprotein Cholesterol ◽

European Ancestry ◽

Randomization Analysis

We performed univariable and multivariable Mendelian randomization (MR) analysis to evaluate the association between blood lipids and risk of atrial fibrillation (AF), including low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), triglyceride (TG), Apolipoprotein A1, and Apolipoprotein B. Methods: Data on the single nucleotide polymorphisms (SNPs) related to blood lipids were obtained from the UK Biobank study with more than 300,000 subjects of White British European ancestry, and data for AF were from the latest meta-analysis of Genome-wide association study (GWASs) with six independent cohorts with more than 1,000,000 subjects of European ancestry. The univariable MR analysis was conducted to explore whether genetic evidence of individual lipid-related traits was significantly associated with AF risks and multivariable MR analysis with three models was performed to assess the independent effects of lipid-related traits. Results: The IVW estimate showed that genetically predicted LDL-C (OR: 1.016, 95% CI: 0.962–1.073, p = 0.560), HDL-C (OR: 0.951, 95% CI: 0.895–1.010, p = 0.102), TG (OR: 0.961, 95% CI: 0.889–1.038, p = 0.313), Apolipoprotein A1 (OR: 0.978, 95% CI: 0.933–1.025, p = 0.356), and Apolipoprotein B (OR: 1.008, 95% CI: 0.959–1.070, p = 0.794) were not causally associated with the risk of AF. Sample mode (OR: 0.852, 95% CI: 0.731–0.993, p = 0.043) and weighted mode (OR: 0.907, 95% CI: 0.841–0.979, p = 0.013) showed that a 1-unit increase in TG (mmol/L) was causally associated with a 14.8% and 9.3% relative decrease in AF risk, respectively. The multivariable MR analysis with model 1, 2, and 3 indicated that TG, LDL-C, HDL-C, Apolipoprotein A1, and Apolipoprotein B were not associated with the lower risk for AF. Conclusions: Our multivariable Mendelian randomization analysis (MVMR) finding suggested no genetic evidence of lipid traits was significantly associated with AF risk. Furthermore, more work is warranted to confirm the potential association between lipid traits and AF risks.

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