Causal association of polyunsaturated fatty acids with chronic pain: a two-sample Mendelian randomization study
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ABSTRACT:
SUBMITTER: Dai Y
PROVIDER: S-EPMC10512421 | biostudies-literature | 2023 Jan
REPOSITORIES: biostudies-literature
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| S-EPMC11243184 | biostudies-literature
Project description:ObjectivesPrevious studies have reported a potential association of polyunsaturated fatty acids (PUFAs) levels with allergic disease risk and the possible benefit of PUFAs supplementation on allergic disease prevention. This study was performed to estimate the genetic association between PUFAs and allergic diseases using the method of both univariable and multivariable two-sample Mendelian randomization (MR).MethodsAs indicators of the PUFAs levels, we included the omega-3, omega-6, docosahexaenoic acid (DHA), eicosapentaenoic acid (EPA), linoleic acid (LA), and the ratio of omega-6 to omega-3 (omega-6:3). Summarized statistics of genome-wide association studies (GWASs) for these PUFAs were obtained from the United Kingdom Biobank and the Twins United Kingdom cohort. Genetic data relating to allergic diseases, including atopic dermatitis (AD), allergic rhinitis (AR), allergic conjunctivitis (AC), allergic urticaria (AU) and asthma, were accessed from the FinnGen biobank analysis. Odds ratios and 95% CIs were used to express the impact.ResultsThe MR results denoted a genetic association between the genetically determined increase in omega-3 levels and the decreased risk of some allergic diseases including AD (OR: 0.863; 95% CI: 0.785 to 0.949; p = 3.86E-03), AC (OR:0.720; 95% CI: 0.547 to 0.947; p = 1.87E-02) and AU (OR:0.821; 95% CI: 0.684 to 0.985; p = 3.42E-02), while omega-6 and DHA level was only found to have negatively correlation with risk of AC with ORs of 0.655 (95% CI: 0.445 to 0.964; p = 3.18E-02) and 0.671 (95% CI 0.490 to 0.918; p = 1.25E-02), respectively. Omega-6:3 were causally significantly associated with the increased risk of AD (OR:1.171; 95% CI: 1.045 to 1.312; p = 6.46E-03) and AC (IVW: OR:1.341; 95% CI: 1.032 to 1.743; p = 2.83E-02). After adjustment of age, economic level, BMI, smoking and alcohol behaviors in the multivariable MR analysis, a direct causal protective effect of omega-3 on AD and AC, as well as a direct causal association between DHA and AD were observed. Omega-6:3 was also found to be directly associated with an increased risk of AD and AC. No association was found of EPA or LA with allergic diseases.ConclusionHigher PUFA concentrations (omega-3, omega-6, DHA) and lower omega-6:3 ratios were genetically associated with a lower risk of some allergic diseases.
| S-EPMC9500587 | biostudies-literature
Project description:BackgroundThis Mendelian randomization (MR) study aimed to explore the causal relationship between polyunsaturated fatty acids (PUFAs) and bone mineral density (BMD).MethodsWe conducted a two-sample MR analysis to figure out if there is any causal effect of PUFAs on BMD through the summary data from the genome-wide association study (GWAS). Relationships were evaluated through inverse variance weighted (IVW), MR-Egger, weighted median, and maximum likelihood methods. The MR Pleiotropy RESidual Sum and Outlier (MR-PRESSO) test was performed to detect the horizontal pleiotropy.ResultsOur findings revealed that omega-6 fatty acids were negatively related to the TB-BMD (beta-estimate: -0.0515; 95% confidence interval [CI]: -0.0911 to -0.0119; standard error [SE]: 0.0201; p-value: 0.0106). The reverse direction MR analysis showed that TB-BMD was linked to the omega-6 FAs (beta-estimate: -0.0699; 95% CI: -0.1304 to -0.0095; SE: 0.0308; p-value: 0.0265). No statistically significant correlations between PUFAs and BMD were observed after adjusting the interactions between metabolites.ConclusionThis two-sample MR analyses produced strong and new genomic evidence that there was a causal relationship between omega-6 FAs and BMD. Further investigations are still required to elucidate the potential mechanism.
| S-EPMC9304696 | biostudies-literature
Project description: Not available
| S-EPMC10490345 | biostudies-literature
Project description:BackgroundThe association between obesity and musculoskeletal chronic pain has attracted much attention these days; however, the causal relationship between them is uncertain. Hence, this study performed a Mendelian randomization (MR) analysis to investigate the causal effects of body mass index (BMI), waist circumference (WC), hip circumference (HC), and waist-to-hip ratio (WHR) on knee pain, hip pain, and back pain.Materials and methodsThe summary data for obesity and musculoskeletal chronic pain came from the genome-wide association study datasets. Significant and independent (p < 5 × 10-8; r2 < 0.001, kb = 10,000) single-nucleotide polymorphisms were extracted for MR analysis. The inverse variance weighted (IVW) and other methods were used for MR analysis, while sensitivity analyses were conducted to test the reliability and stability.ResultsThe positive causal effects of BMI on knee pain (odds ratio (OR) = 1.049; 95% CI: 1.034 to 1.063; p = 9.88 × 10-12), hip pain (OR = 1.034; 95% CI: 1.024 to 1.044; p = 1.38 × 10-12), and back pain (OR = 1.022; 95% CI: 1.007 to 1.038; p = 0.004) were observed. WC and HC were also positively associated with knee pain (WC: OR = 1.057; 95% CI: 1.041 to 1.072; p = 1.54 × 10-13; HC: OR = 1.034; 95% CI: 1.017 to 1.052; p = 1.32 × 10-4) and hip pain (WC: OR = 1.031; 95% CI: 1.020 to 1.042; p = 2.61 × 10-8; HC: OR = 1.027; 95% CI: 1.018 to 1.035; p = 5.48 × 10-10) but not back pain. No causal relationship was found between WHR and musculoskeletal chronic pain. The results were robust according to sensitivity tests.ConclusionsThis study revealed that BMI was positively related to knee, hip, and back pain and that WC and HC were positively associated with knee and hip pain, while WHR was not related to any type of musculoskeletal chronic pain.
| S-EPMC9445165 | biostudies-literature
Project description:In recent years, researchers have examined the use of polyunsaturated fatty acids (PUFA) or a low omega-6/3 ratio to protect the knee joint. The current study is based on genome-wide association study (GWAS) analysis and uses the Mendelian randomization (MR) method to evaluate the effect of total PUFA, omega-3, omega-6, and omega-6/3 ratios on osteoarthritis (OA). First, we downloaded the latest PUFA and OA GWAS data. The PUFA data were divided into four groups: total PUFA, omega-3, omega-6, and omega-6/3 ratios. The OA data were split into nine groups: hip OA (total, males, and females), knee OA (total, males, and females), and hand OA (total, males, and females). Then, qualified SNPs were selected as instrumental variables. Inverse variance weighting (IVW), weighted median, and the MR‒Egger method were used for MR analysis. Finally, MR‒Egger, MR-Presso, and Cochran's Q statistical methods were used to evaluate the heterogeneity and pleiotropy. Thirty-six IVW results showed that total PUFA, omega-3, omega-6, and omega-6/3 ratios did not significantly increase or decrease the risk of knee, hip, and hand OA. The IVW results of the effect of PUFA on OA (male and female) were as follows: total PUFA-knee OA (OR: 0.97, 95% CI: 0.92-1.02, P = 0.283); total PUFA-hip OA (OR: 1.01, 95% CI: 0.93-1.08, P = 0.806); total PUFA-hand OA (OR: 0.99, 95% CI: 0.91-1.07, P = 0.896). There was no obvious horizontal polytropy in all the analyses, and there was heterogeneity in some analyses. Our study does not indicate that total PUFA, mega-3, and low omega-6/3 ratios are helpful for people with OA, nor does it indicate that omega-6 increases the risk of OA. The dietary management of PUFA in OA patients needs to be performed cautiously.
| S-EPMC11840048 | biostudies-literature
Project description:IntroductionDespite numerous observational studies reporting a positive correlation between polyunsaturated fatty acids (PUFAs) and the risk of sepsis and mortality, the causation of such an association has yet to be firmly established. Thus, our study aimed to undertake the Mendelian randomization (MR) approach to scrutinize the potential causalities of PUFAs with sepsis and mortality risk.MethodsWe conducted the MR investigation using genome-wide association study (GWAS) summary statistics of PUFAs [including omega-3 fatty acids (omega-3), omega-6 fatty acids (omega-6), the ratio of omega-6 to omega-3 fatty acids (omega-6:3), docosahexaenoic acid (DHA), linoleic acid (LA)], sepsis, and sepsis mortality. We utilized the GWAS summary data from the UK Biobank. To establish reliable causality, we employed the inverse-variance weighted (IVW) method as the primary analytical approach, together with four additional MR methods. In addition, we performed heterogeneity and horizontal pleiotropy assessments using Cochrane's Q test and MR-Egger intercept test, respectively. Finally, we performed a series of sensitivity analyses to enhance the precision and veracity of our findings.ResultsThe IVW method showed that genetically predicted omega-3 [odd ratio (OR) 0.914, 95% confidence interval (CI) 0.845-0.987, P = 0.023] and DHA (OR 0.893, 95% CI 0.815-0.979, P = 0.015) were suggestively linked to a decreased risk of sepsis. Furthermore, genetically predicted DHA (OR 0.819, 95% CI 0.681-0.986, P = 0.035) was suggestively associated with a reduced risk of sepsis-related death. Conversely, the omega-6:3 ratio (OR 1.177, 95% CI 1.011-1.371, P = 0.036) was suggestively linked to an increased risk of sepsis-induced mortality. On the basis of the MR-Egger intercept assessment, it appears that our MR examination was not influenced by any horizontal pleiotropy (all P > 0.05). Moreover, the reliability of the estimated causal association was confirmed by the sensitivity analyses.ConclusionOur study supported the casual effect between PUFAs and susceptibility to sepsis and sepsis-related death. Our findings underline the importance of specific PUFAs levels, particularly for individuals with a genetic susceptibility to sepsis. Further research is needed to confirm these findings and investigate the underlying mechanisms.
| S-EPMC10390410 | biostudies-literature
Project description:Polyunsaturated fatty acids (PUFAs) affect several physiological processes, including visual acuity, but their relationship with diabetic retinopathy (DR) remains elusive. The aim of this study was to determine whether PUFAs have a causal effect on DR. PUFAs- (total and omega-3 [FAw3] and omega-6 [FAw6] fatty acids and their ratio) and DR-associated single nucleotide polymorphisms derived from genome-wide association studies; sample sizes were 114,999 for fatty acids and 216,666 for any DR (ADR), background DR (BDR), severe non-proliferative DR (SNPDR), and proliferative DR (PDR). We hypothesized that the intra-body levels of PUFAs have an impact on DR and conducted a two-sample Mendelian randomization (MR) study to assess the causality. Pleiotropy, heterogeneity, and sensitivity analyses were performed to verify result reliability. High levels of PUFAs were found to be associated with reduced risk of both ADR and PDR. Moreover, FAw3 was associated with a decreased risk of PDR, whereas FAw6 demonstrated an association with lowered risks of both BDR and PDR. Our findings provide genetic evidence, for the first time, for a causal relationship between PUFAs and reduced DR risk. Consequently, our comprehensive MR analysis strongly urges further investigation into the precise functions and long-term effects of PUFAs, FAw3, and FAw6 on DR.
| S-EPMC10574403 | biostudies-literature
Project description:IntroductionObservational studies demonstrated controversial effect of polyunsaturated fatty acids (PUFAs) on Parkinson's disease (PD) with limited causality evidence. Randomized control trials showed possible improvement in PD symptoms with PUFA supplement but had small study population and limited intervention time.MethodsA two-sample Mendelian randomization was designed to evaluate the causal relevance between PUFAs and PD, using genetic variants of PUFAs as instrumental variables and PD data from the largest genome-wide association study as outcome. Inverse variance weighted (IVW) method was applied to obtain the primary outcome. Mendelian randomization Egger regression, weighted median and weighted mode methods were exploited to assist result analyses. Strict Mendelian randomization and multivariable Mendelian randomization (MVMR) were used to estimate direct effects of PUFAs on PD, eliminating pleiotropic effect. Debiased inverse variance weighted estimator was implemented when weak instrument bias was introduced into the analysis. A variety of sensitivity analyses were utilized to assess validity of the results.ResultsOur study included 33,674 PD cases and 449,056 controls. Higher plasma level of arachidonic acid (AA) was associated with a 3% increase of PD risk per 1-standard deviation (SD) increase of AA (IVW; Odds ratio (OR)=1.03 [95% confidence interval (CI) 1.01-1.04], P = 2.24E-04). After MVMR (IVW; OR=1.03 [95% CI 1.02-1.04], P =6.15E-08) and deletion of pleiotropic single-nucleotide polymorphisms overlapping with other lipids (IVW; OR=1.03 [95% CI 1.01-1.05], P =5.88E-04), result was still significant. Increased level of eicosapentaenoic acid (EPA) showed possible relevance with increased PD risk after adjustment of pleiotropy (MVMR; OR=1.05 [95% CI 1.01-1.08], P =5.40E-03). Linoleic acid (LA), docosahexaenoic acid (DHA), docosapentaenoic acid (DPA) and alpha-linolenic acid (ALA) were found not causally relevant to PD risk. Various sensitivity analyses verified the validity of our results. In conclusion, our findings from Mendelian randomization suggested that elevated levels of AA and possibly EPA might be linked to a higher risk of PD. No association between PD risk and LA, DHA, DPA, or ALA was found.DiscussionThe odds ratio for plasma AA and PD risk was weak. It is important to approach our results with caution in clinical practice and to conduct additional studies on the relationship between PUFAs and PD risk.
| S-EPMC9992541 | biostudies-literature
Project description:BackgroundPrevious observational studies have found that lower levels of circulating polyunsaturated fatty acids (PUFAs) were associated with a higher risk of sleep apnea (SA). However, the causality of the association remains unclear.Materials and methodsWe used the two-sample Mendelian randomization (MR) study to assess the causal association of omega-3 and omega-6 fatty acids with SA. Single-nucleotide polymorphisms (SNPs) predicting the plasma level of PUFAs at the suggestive genome-wide significance level (p < 5 × 10-6) were selected as instrumental variables (IVs) from the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) (n = ∼8,000) Consortium. For outcomes, the summary-level statistics of SA were obtained from the latest genome-wide association study (GWAS), which combined five cohorts with a total number of 25,008 SA cases and 172,050 snoring cases (total = 523,366).ResultsWe found no association of α-linolenic acid (ALA) [odds ratio (OR) = 1.09 per% changed, 95% confidence interval (CI) 0.67-1.78], eicosapentaenoic acid (EPA) (OR = 0.94, 95% CI 0.88-1.01), docosapentaenoic acid (DPA) (OR = 0.95, 95% CI 0.88-1.02), and docosahexaenoic acid (DHA) (OR = 0.99, 95% CI 0.96-1.02) with the risk of SA using inverse-variance weighted (IVW) method. Moreover, for omega-6 PUFAs, no association between linoleic acid (LA) (OR = 0.98, 95% CI 0.96-1.01), arachidonic acid (AA) (1.00, 95% CI 0.99-1.01), and adrenic acid (AdrA) (0.93, 95% CI 0.71-1.21) with the risk of SA was found. Similarly, no associations of PUFAs with SA were found in single-locus MR analysis.ConclusionIn the current study, we first found that there is no genetic evidence to support the causal role of omega-3 and omega-6 PUFAs in the risk of SA. From a public health perspective, our findings refute the notion that consumption of foods rich in PUFAs or the use of PUFAs supplementation can reduce the risk of SA.
| S-EPMC9433775 | biostudies-literature