Associations between polyunsaturated fatty acid concentrations and Parkinson’s disease: A two-sample Mendelian randomization study
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...
| Main Authors: | , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2023-02-01
|
| Series: | Frontiers in Aging Neuroscience |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fnagi.2023.1123239/full |
| _version_ | 1797900465915035648 |
|---|---|
| author | Xue Zhu Sijia Huang Wenyan Kang Peizhan Chen Jun Liu Jun Liu |
| author_facet | Xue Zhu Sijia Huang Wenyan Kang Peizhan Chen Jun Liu Jun Liu |
| author_sort | Xue Zhu |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-04-10T08:45:23Z |
| format | Article |
| id | doaj.art-0361662d6cea489fab27bdbae0ded8b7 |
| institution | Directory Open Access Journal |
| issn | 1663-4365 |
| language | English |
| last_indexed | 2024-04-10T08:45:23Z |
| publishDate | 2023-02-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Aging Neuroscience |
| spelling | doaj.art-0361662d6cea489fab27bdbae0ded8b72023-02-22T07:56:27ZengFrontiers Media S.A.Frontiers in Aging Neuroscience1663-43652023-02-011510.3389/fnagi.2023.11232391123239Associations between polyunsaturated fatty acid concentrations and Parkinson’s disease: A two-sample Mendelian randomization studyXue Zhu0Sijia Huang1Wenyan Kang2Peizhan Chen3Jun Liu4Jun Liu5Department of Neurology and Institute of Neurology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaDepartment of Neurology and Institute of Neurology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaDepartment of Neurology and Institute of Neurology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaDepartment of General Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaDepartment of Neurology and Institute of Neurology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaCo-innovation Center of Neuroregeneration, Nantong University, Nantong, ChinaIntroductionObservational 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.https://www.frontiersin.org/articles/10.3389/fnagi.2023.1123239/fullpolyunsaturated fatty acidsParkinson’s diseaseMendelian randomizationcausalitydietary modification |
| spellingShingle | Xue Zhu Sijia Huang Wenyan Kang Peizhan Chen Jun Liu Jun Liu Associations between polyunsaturated fatty acid concentrations and Parkinson’s disease: A two-sample Mendelian randomization study Frontiers in Aging Neuroscience polyunsaturated fatty acids Parkinson’s disease Mendelian randomization causality dietary modification |
| title | Associations between polyunsaturated fatty acid concentrations and Parkinson’s disease: A two-sample Mendelian randomization study |
| title_full | Associations between polyunsaturated fatty acid concentrations and Parkinson’s disease: A two-sample Mendelian randomization study |
| title_fullStr | Associations between polyunsaturated fatty acid concentrations and Parkinson’s disease: A two-sample Mendelian randomization study |
| title_full_unstemmed | Associations between polyunsaturated fatty acid concentrations and Parkinson’s disease: A two-sample Mendelian randomization study |
| title_short | Associations between polyunsaturated fatty acid concentrations and Parkinson’s disease: A two-sample Mendelian randomization study |
| title_sort | associations between polyunsaturated fatty acid concentrations and parkinson s disease a two sample mendelian randomization study |
| topic | polyunsaturated fatty acids Parkinson’s disease Mendelian randomization causality dietary modification |
| url | https://www.frontiersin.org/articles/10.3389/fnagi.2023.1123239/full |
| work_keys_str_mv | AT xuezhu associationsbetweenpolyunsaturatedfattyacidconcentrationsandparkinsonsdiseaseatwosamplemendelianrandomizationstudy AT sijiahuang associationsbetweenpolyunsaturatedfattyacidconcentrationsandparkinsonsdiseaseatwosamplemendelianrandomizationstudy AT wenyankang associationsbetweenpolyunsaturatedfattyacidconcentrationsandparkinsonsdiseaseatwosamplemendelianrandomizationstudy AT peizhanchen associationsbetweenpolyunsaturatedfattyacidconcentrationsandparkinsonsdiseaseatwosamplemendelianrandomizationstudy AT junliu associationsbetweenpolyunsaturatedfattyacidconcentrationsandparkinsonsdiseaseatwosamplemendelianrandomizationstudy AT junliu associationsbetweenpolyunsaturatedfattyacidconcentrationsandparkinsonsdiseaseatwosamplemendelianrandomizationstudy |