Dataset Information

Polyunsaturated Fatty Acids Level and Bone Mineral Density: A Two-Sample Mendelian Randomization Study.

ABSTRACT:

Background

This Mendelian randomization (MR) study aimed to explore the causal relationship between polyunsaturated fatty acids (PUFAs) and bone mineral density (BMD).

Methods

We 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.

Results

Our 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.

Conclusion

This 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.

SUBMITTER: Wang L

PROVIDER: S-EPMC9304696 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature

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Publications

Polyunsaturated Fatty Acids Level and Bone Mineral Density: A Two-Sample Mendelian Randomization Study.

Wang Lin L Zhang Chao C Liang Hao H Zhou Nian N Huang Tianji T Zhao Zenghui Z Luo Xiaoji X

Frontiers in endocrinology 20220708

<h4>Background</h4>This Mendelian randomization (MR) study aimed to explore the causal relationship between polyunsaturated fatty acids (PUFAs) and bone mineral density (BMD).<h4>Methods</h4>We 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 Ple ...[more]

PMID: 35872990

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Project description:BackgroundPolyunsaturated fatty acids (PUFAs) are closely related to osteoporosis. To test their causal relationship, we conducted a Mendelian randomization (MR) analysis.MethodsWe analyzed the causal relationship between four PUFAs measures, n-3 PUFAs (n-3), n-6 PUFAs (n-6), the ratio of n-3 PUFAs to total fatty acids (n-3 pct), and the ratio of n-6 PUFAs to n-3 PUFAs (n-6 to n-3), and five measures of osteoporosis, including estimated bone mineral density (eBMD), forearm (FA) BMD, femoral neck (FN) BMD, lumbar spine (LS) BMD, and fracture, using two-sample MR analysis. In order to verify the direct effect between PUFAs and BMD, we chose interleukin-6 (IL-6), tumor necrosis factor-β (TNF-β), and bone morphogenetic proteins 7 (BMP-7), three markers or cytokines strongly related to BMD, as possible confounding factors, and analyzed the possible causal relationships between them and PUFAs or BMD by MR. Inverse variance weighting (IVW), MR-Egger, weighted and weighted median were conducted. MR Pleiotropy RESidual Sum and Outlier (MR-PRESSO) and MR-Egger regression methods were used to evaluate the potential pleiotropy of instrumental variables (IVs) and outliers were identified by MR-PRESSO. Cochran's Q statistic was used to detect the heterogeneity among IVs. Leave-one-out sensitivity analysis was used to find SNPs that have a significant impact on the results. All results were corrected by the Bonferroni correction.ResultsThe IVW results showed that n-3 PUFAs (OR = 1.030, 95% CI: 1.013, 1.047, P = 0.001) and n-6 PUFAs (OR = 1.053, 95% CI: 1.034, 1.072, P < 0.001) were positively correlated with eBMD, while n-6 to n-3 (OR = 0.947, 95% CI: 0.924, 0.970, P < 0.001) were negatively correlated with eBMD. These casual relationships still existed after Bonferroni correction. There were positive effects of n-3 PUFAs on FA BMD (OR = 1.090, 95% CI: 1.011, 1.176, P = 0.025) and LS BMD (OR = 1.056, 95% CI: 1.011, 1.104, P = 0.014), n-3 pct on eBMD (OR = 1.028, 95% CI: 1.002, 1.055, P = 0.035) and FA BMD (OR = 1.090, 95% CI: 1.011, 1.174, P = 0.025), n-6 to n-3 on LS BMD (OR = 1.071, 95% CI: 1.021, 1.124, P = 0.005); negative effects of n-3 pct on fracture (OR = 0.953, 95% CI: 0.918, 0.988, P = 0.009) and n-6 to n-3 on FA BMD (OR = 0.910, 95% CI: 0.837, 0.988, P = 0.025). However, these causal effects all disappeared after Bonferroni correction (all P > 0.0025). None of IL-6, TNF-β, and BMP-7 had a causal effect on PUFA and BMD simultaneously (all P > 0.05).ConclusionEvidence from this MR study supports the genetically predicted causal effects of n-3, n-6, n-3 pct, and n-6 to n-3 on eBMD. In addition, n-3 not only associate with FA BMD and LS BMD through its own level and n-6 to n-3, but also link to fracture through n-3 pct.

Project description:BackgroundObservational studies have indicated an association between polyunsaturated fatty acids (PUFAs) and chronic pain, but the potential causal link remains controversial. Here, we aimed to investigate whether a causal relationship exists between the concentration of circulating PUFAs and chronic pain as well as the direction of this association.MethodsWe collected statistical data from relevant genome-wide association studies to explore the causal link between four PUFAs, along with the ratio of omega-6 fatty acids (FAs) to omega-3 FAs (omega-6:3 ratio), and chronic pain in eight specific body parts. We used the inverse-variance weighting (IVW) method for two-sample Mendelian randomization (MR) analysis and conducted supplementary analyses using four other methods (MR-Egger, weighted median, weighted mode, and simple mode). To verify the robustness of the MR study, we performed multiple sensitivity analyses.ResultsThe results revealed a negative correlation between omega-3 FAs [IVW, OR 95% CI: 0.952 (0.914, 0.991), p = 0.017] and docosahexaenoic acid (DHA) [IVW, OR 95% CI: 0.935 (0.893, 0.978), p = 0.003] with abnormal and pelvic pain. Furthermore, a positive correlation was observed between the omega-6:3 ratio [IVW, OR 95% CI: 1.057 (1.014, 1.101), p = 0.009] with abdominal and pelvic pain. Additionally, we found a negative correlation between omega-3 FAs [IVW, OR 95% CI: 0.947 (0.902, 0.994), p = 0.028] and lower back pain or sciatica. However, no causal relationship was found between the concentration of circulating PUFAs and pain in other body parts, including the face, throat and chest, joints, limbs, lower back, and gynecological parts. The robustness of these MR results was verified through multi-validity and retention method analyses.ConclusionOur analysis suggests that higher circulating concentrations of omega-3 FAs and DHA and a lower omega-6:3 ratio are associated with a reduced risk of abdominal and pelvic pain. Additionally, a higher concentration of circulating omega-3 FAs is linked to a reduced risk of lower back pain and/or sciatica. These findings have major implications for the targeted prevention and treatment of chronic pain using PUFAs.

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.

Project description:BackgroundResults from epidemiologic studies examining polyunsaturated fatty acids (PUFA) and colorectal cancer risk are inconsistent. Mendelian randomization may strengthen causal inference from observational studies. Given their shared metabolic pathway, examining the combined effects of aspirin/NSAID use with PUFAs could help elucidate an association between PUFAs and colorectal cancer risk.MethodsInformation was leveraged from genome-wide association studies (GWAS) regarding PUFA-associated SNPs to create weighted genetic scores (wGS) representing genetically predicted circulating blood PUFAs for 11,016 non-Hispanic white colorectal cancer cases and 13,732 controls in the Genetics and Epidemiology of Colorectal Cancer Consortium (GECCO). Associations per SD increase in the wGS were estimated using unconditional logistic regression. Interactions between PUFA wGSs and aspirin/NSAID use on colorectal cancer risk were also examined.ResultsModest colorectal cancer risk reductions were observed per SD increase in circulating linoleic acid [ORLA = 0.96; 95% confidence interval (CI) = 0.93-0.98; P = 5.2 × 10-4] and α-linolenic acid (ORALA = 0.95; 95% CI = 0.92-0.97; P = 5.4 × 10-5), whereas modest increased risks were observed for arachidonic (ORAA = 1.06; 95% CI = 1.03-1.08; P = 3.3 × 10-5), eicosapentaenoic (OREPA = 1.04; 95% CI = 1.01-1.07; P = 2.5 × 10-3), and docosapentaenoic acids (ORDPA = 1.03; 95% CI = 1.01-1.06; P = 1.2 × 10-2). Each of these effects was stronger among aspirin/NSAID nonusers in the stratified analyses.ConclusionsOur study suggests that higher circulating shorter-chain PUFAs (i.e., LA and ALA) were associated with reduced colorectal cancer risk, whereas longer-chain PUFAs (i.e., AA, EPA, and DPA) were associated with an increased colorectal cancer risk.ImpactThe interaction of PUFAs with aspirin/NSAID use indicates a shared colorectal cancer inflammatory pathway. Future research should continue to improve PUFA genetic instruments to elucidate the independent effects of PUFAs on colorectal cancer.

Project description:BackgroundObservational studies and clinical trials have implicated polyunsaturated fatty acids (PUFAs) in potentially safeguarding against diabetic microvascular complication. Nonetheless, the causal nature of these relationships remains ambiguous due to conflicting findings across studies. This research employs Mendelian randomization (MR) to assess the causal impact of PUFAs on diabetic microvascular complications.MethodsWe identified instrumental variables for PUFAs, specifically omega-3 and omega-6 fatty acids, using the UK Biobank data. Outcome data regarding diabetic microvascular complications were sourced from the FinnGen Study. Our analysis covered microvascular outcomes in both type 1 and type 2 diabetes, namely diabetic neuropathy (DN), diabetic retinopathy (DR), and diabetic kidney disease (DKD). An inverse MR analysis was conducted to examine the effect of diabetic microvascular complications on PUFAs. Sensitivity analyses were performed to validate the robustness of the results. Finally, a multivariable MR (MVMR) analysis was conducted to determine whether PUFAs have a direct influence on diabetic microvascular complications.ResultsThe study indicates that elevated levels of genetically predicted omega-6 fatty acids substantially reduce the risk of DN in type 2 diabetes (odds ratio (OR): 0.62, 95% confidence interval (CI): 0.47-0.82, p = 0.001). A protective effect against DR in type 2 diabetes is also suggested (OR: 0.75, 95% CI: 0.62-0.92, p = 0.005). MVMR analysis confirmed the stability of these results after adjusting for potential confounding factors. No significant effects of omega-6 fatty acids were observed on DKD in type 2 diabetes or on any complications in type 1 diabetes. By contrast, omega-3 fatty acids showed no significant causal links with any of the diabetic microvascular complications assessed.ConclusionsOur MR analysis reveals a causal link between omega-6 fatty acids and certain diabetic microvascular complications in type 2 diabetes, potentially providing novel insights for further mechanistic and clinical investigations into diabetic microvascular complications.

Dataset Information

Polyunsaturated Fatty Acids Level and Bone Mineral Density: A Two-Sample Mendelian Randomization Study.

Background

Methods

Results

Conclusion

Publications

Polyunsaturated Fatty Acids Level and Bone Mineral Density: A Two-Sample Mendelian Randomization Study.

Similar Datasets

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