Causal association of polyunsaturated fatty acids with chronic pain: a two-sample Mendelian randomization study

Dai, Yuxuan; Chen, Yu; Gu, Rui; Zhang, Chao; Jiang, Rui

doi:10.3389/fnut.2023.1265928

Cited by 3 publications

(2 citation statements)

References 43 publications

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“…To ensure comprehensive results, IVs for PUFAs concentrations were obtained using p < 5 × 10 −8 , as per previous research ( 32 ). Additionally, to minimize the impact of linkage disequilibrium (LD), a clumping process with R 2 = 0.001 and a genetic distance of 10,000 kb was applied using the R package.…”

Section: Methodsmentioning

confidence: 99%

“…Specifically, when exposed to the UK Biobank, researchers frequently opt to complement this with outcome data from the FinnGen Biobank. For example, Dai et al ( 32 ) investigate whether a causal relationship exists between the concentration of circulating PUFAs and chronic pain as well as the direction of this association. In the GWAS data section, GWAS data on circulating PUFA concentrations (exposures) were obtained from the UK Biobank and included 114,999 European participants.…”

Section: Limitations and Strengthsmentioning

confidence: 99%

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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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Section: Methodsmentioning

confidence: 99%

Section: Limitations and Strengthsmentioning

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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Chronic Low Back Pain Causal Risk Factors Identified by Mendelian Randomization: a Cross-Sectional Cohort Analysis

Zheng,

Scheffler,

Ewing

et al. 2024

Preprint

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Background Context: There are a number of risk factors- from biological, psychological, and social domains- for non-specific chronic low back pain (cLBP). Many cLBP treatments target risk factors on the assumption that the targeted factor is not just associated with cLBP but is also a cause (i.e, a causal risk factor). In most cases this is a strong assumption, primarily due to the possibility of confounding variables. False assumptions about the causal relationships between risk factors and cLBP likely contribute to the generally marginal results from cLBP treatments. Purpose: The objectives of this study were to a) using rigorous confounding control compare associations between modifiable causal risk factors identified by Mendelian randomization (MR) studies with associations in a cLBP population and b) estimate the association of these risk factors with cLBP outcomes. Study Design/Setting: Cross sectional analysis of a longitudinal, online, observational study. Patient Sample: 1,376 participants in BACKHOME, a longitudinal observational e- Cohort of U.S. adults with cLBP that is part of the NIH Back Pain Consortium (BACPAC) Research Program. Outcome Measures: Pain, Enjoyment of Life, and General Activity (PEG) Scale. Methods: Five risk factors were selected based on evidence from MR randomization studies: sleep disturbance, depression, BMI, alcohol use, and smoking status. Confounders were identified using the ESC-DAG approach, a rigorous method for building directed acyclic graphs based on causal criteria. Strong evidence for confounding was found for age, female sex, education, relationship status, financial strain, anxiety, fear avoidance and catastrophizing. These variables were used to determine the adjustment sets for the primary analysis. Potential confounders with weaker evidence were used for a sensitivity analysis. Results: Participants had the following characteristics: age 54.9 +/- 14.4 years, 67.4% female, 60% never smokers, 29.9% overweight, 39.5% obese, PROMIS sleep disturbance T-score 54.8 +/- 8.0, PROMIS depression T-score 52.6 +/- 10.1, Fearavoidance Beliefs Questionnaire 11.6 +/- 5.9, Patient Catastrophizing Scale 4.5 +/- 2.6, PEG 4.4 +/- 2.2. In the adjusted models alcohol use, sleep disturbance, depression, and obesity were associated with PEG, after adjusting for confounding variables identified via a DAG constructed using a rigorous protocol. The adjusted effect estimates- the expected change in the PEG outcome for every standard deviation increase or decrease in the exposure (or category shift for categorical exposures) were the largest for sleep disturbance and obesity. Each SD increase in the PROMIS sleep disturbance T-score resulted in a mean 0.77 (95% CI: 0.66, 0.88) point increase in baseline PEG score. Compared to participants with normal BMI, adjusted mean PEG score was slightly higher by 0.37 points (95% CI: 0.09, 0.65) for overweight participants, about 0.8 to 0.9 points higher for those in obesity classes I and II, and 1.39 (95% CI: 0.98, 1.80) points higher for the most obese participants. Each SD increase in the PROMIS depression T-score was associated with a mean 0.28 (95% CI: 0.17, 0.40) point increase in baseline PEG score, while each SD decrease in number of alcoholic drinks per week resulted in a mean 0.12 (95%CI: 0.01, 0.23) increase in baseline PEG score in the adjusted model. Conclusions: Several modifiable causal risk factors for cLBP - alcohol use, sleep disturbance, depression, and obesity- are associated with PEG, after adjusting for confounding variables identified via a DAG constructed using a rigorous protocol. Convergence of our findings for sleep disturbance, depression, and obesity with the results from MR studies, which have different designs and biases, strengthens the evidence for causal relationships between these risk factors and cLBP (1). The estimated effect of change in a risk factors on change in PEG were the largest for sleep disturbance and obesity. Future analyses will evaluate these relationships with longitudinal data.

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Nutritional Strategies for Chronic Craniofacial Pain and Temporomandibular Disorders: Current Clinical and Preclinical Insights

Piriyaprasath,

Kakihara,

Hasegawa

et al. 2024

Nutrients

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This narrative review provides an overview of current knowledge on the impact of nutritional strategies on chronic craniofacial pain associated with temporomandibular disorders (TMDs). Individuals experiencing painful TMDs alter their dietary habits, avoiding certain foods, possibly due to chewing difficulties, which might lead to nutrient deficiencies. Our literature investigation revealed that the causal links between nutritional changes and craniofacial pain remain unclear. However, clinical and preclinical studies suggest that nutraceuticals, including vitamins, minerals, polyphenols, omega-3 fatty acids, isoprenoids, carotenoids, lectins, polysaccharides, glucosamines, and palmitoylethanolamides, could have beneficial effects on managing TMDs. This is described in 12 clinical and 38 preclinical articles since 2000. Clinical articles discussed the roles of vitamins, minerals, glucosamine, and palmitoylethanolamides. The other nutraceuticals were assessed solely in preclinical studies, using TMD models, mostly craniofacial inflammatory rodents, with 36 of the 38 articles published since 2013. Our investigation indicates that current evidence is insufficient to assess the efficacy of these nutraceuticals. However, the existing data suggest potential for therapeutic intervention in TMDs. Further support from longitudinal and randomized controlled studies and well-designed preclinical investigations is necessary to evaluate the efficacy of each nutraceutical intervention and understand their underlying mechanisms in TMDs.

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Causal association of polyunsaturated fatty acids with chronic pain: a two-sample Mendelian randomization study

Cited by 3 publications

References 43 publications

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

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

Chronic Low Back Pain Causal Risk Factors Identified by Mendelian Randomization: a Cross-Sectional Cohort Analysis

Nutritional Strategies for Chronic Craniofacial Pain and Temporomandibular Disorders: Current Clinical and Preclinical Insights

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