Plasma polyunsaturated fatty acid concentrations and sleep apnea risk: A two-sample Mendelian randomization study

Wang, Jiao; Huang, Yingyue; Yang, Huiling; Lin, Zihong; Campos, Adrián I.; Rentería, Miguel E.; Lin, Xu

doi:10.3389/fnut.2022.956900

Cited by 3 publications

(3 citation statements)

References 45 publications

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“…Numerous previous studies have employed MR to determine the causal relationship between LA and various diseases, including but not limited to cardiovascular diseases, sleep apnea, and sepsis (22)(23)(24). However, current evidence regarding linoleic acid and T2D primarily stems from cohort studies, with results and views exhibiting evident contradictions and conflicts (10)(11)(12)(13)(14).…”

Section: Discussionmentioning

confidence: 99%

Causal relationship between linoleic acid and type 2 diabetes and glycemic traits: a bidirectional Mendelian randomization study

Liang,

Mu,

Zhang

et al. 2023

Front. Endocrinol.

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ObjectiveTo investigate the causal relationships between linoleic acid and type 2 diabetes, and between linoleic acid and glycemic traits in European populations.MethodsThis study employed a two-sample Mendelian randomization approach to infer causality between linoleic acid and type 2 diabetes, as well as between linoleic acid and glycemic traits, leveraging genetic variations. Data were sourced from genome-wide association study summary datasets. Random-effects inverse-variance weighted, weighted median, and MR-Egger methods were used for the two-sample Mendelian randomization analyses. Results were presented as odds ratios with a 95% confidence interval. Multiple sensitivity analyses were conducted to assess result robustness.ResultsMR findings indicated a correlation between linoleic acid levels and the risk of type 2 diabetes, fasting blood glucose, and glycated hemoglobin (HbA1c), but not with fasting insulin. Specifically: type 2 diabetes (OR: 0.811, 95% CI: 0.688–0.956, P=0.013<0.05),fasting blood glucose (β_IVW): -0.056, 95% CI: (-0.091,-0.021), P=0.002< 0.0125), glycated hemoglobin (β_IVW: -0.032, 95% CI: (-0.048,-0.015), P=0.0002< 0.0125) and Fasting insulin (β_IVW: -0.024, 95% CI: (-0.056,-0.008), P=0.136 >0.05).Reverse MR analyses showed a correlation between type 2 diabetes and reduced levels of linoleic acid (β_IVW: -0.033, 95% CI: (-0.059,-0.006), P=0.014<0.05). Multiple sensitivity analyses also detected study heterogeneity but found no evidence of horizontal pleiotropy.ConclusionHigh levels linoleic acid can reduce the risk of type 2 diabetes, fasting blood glucose, and glycated hemoglobin, but has no significant relation with fasting insulin. Type 2 diabetes can lower linoleic acid levels; however, no significant causal relationship was observed between the three glycemic traits and reduced levels of linoleic acid.

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Section: Discussionmentioning

confidence: 99%

Causal relationship between linoleic acid and type 2 diabetes and glycemic traits: a bidirectional Mendelian randomization study

Liang,

Mu,

Zhang

et al. 2023

Front. Endocrinol.

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“…In this research, the chosen SNPs related to total omega-3, DHA, EPA, total omega-6, LA, and AA were located within or in close proximity to genes involved in lipid transport and metabolism in a broader sense ( Supplementary Files 3–8 ). Consequently, traits associated with lipid metabolism, such as BMI, HDL, LDL, and triglycerides, are considered potential confounders for the risk of ARDs ( 40 ). BMI data were obtained by analyzing results from the largest meta-analysis of genome-wide association studies (GWASs) for BMI, which included summary statistics from the Genetic Investigation of Anthropometric Traits (GIANT) consortium ( 41 ) combined with GWAS data on BMI from UK Biobank participants of European descent, totaling approximately 700,000 individual ( 42 ).…”

Section: Methodsmentioning

confidence: 99%

Assessment of causal relationships between omega-3 and omega-6 polyunsaturated fatty acids in autoimmune rheumatic diseases: a brief research report from a Mendelian randomization study

Xu,

Zakeri

et al. 2024

Front. Nutr.

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BackgroundCurrently, the association between the consumption of polyunsaturated fatty acids (PUFAs) and the susceptibility to autoimmune rheumatic diseases (ARDs) remains conflict and lacks substantial evidence in various clinical studies. To address this issue, we employed Mendelian randomization (MR) to establish causal links between six types of PUFAs and their connection to the risk of ARDs.MethodsWe retrieved summary-level data on six types of PUFAs, and five different types of ARDs from publicly accessible GWAS statistics. Causal relationships were determined using a two-sample MR analysis, with the IVW approach serving as the primary analysis method. To ensure the reliability of our research findings, we used four complementary approaches and conducted multivariable MR analysis (MVMR). Additionally, we investigated reverse causality through a reverse MR analysis.ResultsOur results indicate that a heightened genetic predisposition for elevated levels of EPA (ORIVW: 0.924, 95% CI: 0.666–1.283, PIVW = 0.025) was linked to a decreased susceptibility to psoriatic arthritis (PsA). Importantly, the genetically predicted higher levels of EPA remain significantly associated with an reduced risk of PsA, even after adjusting for multiple testing using the FDR method (PIVW–FDR–corrected = 0.033) and multivariable MR analysis (PMV-IVW < 0.05), indicating that EPA may be considered as the risk-protecting PUFAs for PsA. Additionally, high levels of LA showed a positive causal relationship with a higher risk of PsA (ORIVW: 1.248, 95% CI: 1.013–1.538, PIVW = 0.037). It is interesting to note, however, that the effects of these associations were weakened in our MVMR analyses, which incorporated adjustment for lipid profiles (PMV-IVW> 0.05) and multiple testing using the FDR method (PIVW–FDR–corrected = 0.062). Moreover, effects of total omega-3 PUFAs, DHA, EPA, and LA on PsA, were massively driven by SNP effects in the FADS gene region. Furthermore, no causal association was identified between the concentrations of other circulating PUFAs and the risk of other ARDs. Further analysis revealed no significant horizontal pleiotropy and heterogeneity or reverse causality.ConclusionOur comprehensive MR analysis indicated that EPA is a key omega-3 PUFA that may protect against PsA but not other ARDs. The FADS2 gene appears to play a central role in mediating the effects of omega-3 PUFAs on PsA risk. These findings suggest that EPA supplementation may be a promising strategy for preventing PsA onset. Further well-powered epidemiological studies and clinical trials are warranted to explore the potential mechanisms underlying the protective effects of EPA in PsA.

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“…MR analysis can reduce confounding factors by incorporating genetic markers as instrumental variables (IVs) through random segregation and an independent assortment of genetic polymorphisms during conception ( 19 , 20 ). Causality exploration is made possible by large-scale genome-wide association studies (GWAS) ( 21 ). To assess the causal relationship between the gut microbiota and hypothyroidism, a two-sample MR analysis was conducted using summary statistics from GWAS conducted by the MiBioGen and FinnGen consortia.…”

Section: Introductionmentioning

confidence: 99%

Cross-talk between the gut microbiota and hypothyroidism: a bidirectional two-sample Mendelian randomization study

Shi,

Chen,

et al. 2024

Front. Nutr.

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BackgroundMultiple observational studies suggest a connection between the composition of the gut microbiota and hypothyroidism. However, it has yet to be determined whether the gut microbiota has a causal effect on hypothyroidism.MethodsTo investigate the connection between the gut microbiota and hypothyroidism, two-sample Mendelian randomization was performed using data from a genome-wide association study meta-analysis (n = 18,430) conducted by the MiBioGen consortium. Summary statistics for hypothyroidism (26,342 cases and 59,827 controls) were obtained using the data from the FinnGen consortium R8 release data. To investigate the causal link between the gut microbiota and hypothyroidism, various methods, including MR-Egger, weighted median, weighted model, simple model, MR-PRESSO, and inverse variance weighted (IVW), were employed. The bacteria that were causally linked to hypothyroidism in forward Mendelian randomization analysis were subjected to reverse Mendelian randomization analysis. Cochran’s Q statistics were utilized to gauge the heterogeneity of the instrumental variables.ResultsThe results indicated that Akkermansia had a positive impact on hypothyroidism, with an odds ratio of 0.84 (95% CI 0.74–0.95, p = 0.01) based on the inverse variance-weighted estimates. Additionally, Anaerostipes (OR = 1.17, 95% CI 1.01–1.36, p = 0.04), Butyrivibrio (OR = 0.93, 95% CI 0.88–0.99, p = 0.02), Holdemania (OR = 0.89, 95% CI 0.81–0.99, p = 0.03), Intestinimonas (OR = 1.13, 95% CI 1.02–1.26, p = 0.03), Ruminiclostridium5 (OR = 1.19, 95% CI 1.01–1.41, p = 0.04), and Ruminococcaceae UCG-011 (OR = 0.91, 95% CI 0.84–0.99, p = 0.03) were identified. The gut microbiota was not significantly affected by hypothyroidism, as indicated by the results of the reverse MR analysis. There was no significant variation in the instrumental variables or horizontal pleiotropy.ConclusionThe findings of this study using two-sample Mendelian randomization indicate a causal relationship between Akkermansia and hypothyroidism. Increased Akkermansia inhibits the onset and progression of hypothyroidism. Additional randomized controlled experiments are necessary to elucidate the beneficial impact of probiotics on hypothyroidism and their distinct protective mechanisms.

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Plasma polyunsaturated fatty acid concentrations and sleep apnea risk: A two-sample Mendelian randomization study

Cited by 3 publications

References 45 publications

Causal relationship between linoleic acid and type 2 diabetes and glycemic traits: a bidirectional Mendelian randomization study

Causal relationship between linoleic acid and type 2 diabetes and glycemic traits: a bidirectional Mendelian randomization study

Assessment of causal relationships between omega-3 and omega-6 polyunsaturated fatty acids in autoimmune rheumatic diseases: a brief research report from a Mendelian randomization study

Cross-talk between the gut microbiota and hypothyroidism: a bidirectional two-sample Mendelian randomization study

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