Assessment Of Nutrients And Serum Lipids For Parkinson’s Disease:A Phenome-wide Mendelian Randomization Analysis

Objective:To explore potential causality between nutrients and serum lipids and risk of Parkinson’s disease using Mendelian randomization（MR）analysis.Methods:The instrumental variables（IVs）of nutrients and serum lipids were identified from genome wide association study（GWAS）.In the United kingdom biobank（UK Biobank）,single nucleotide polymorphisms（SNPs）satisfying P<5×10^-8 were matched as IVs of Parkinson’s disease in MR analysis.In this study,R language was used for MR analysis,and Mendelian randomization Method of Inverse variance weighted（MR-IVW Method）was used as the main analysis method.In order to ensure the accuracy of the results,this study also used two methods based on Mendelian randomization Method of simple median based（MR-SM Method）and Mendelian randomization Method of weighted median based（MR-WM Method）to explore potential causality between nutrients and serum lipids and risk of Parkinson’s disease.Results:1.After screening,16 nutrients and 4 serum lipids were included in the analysis.Totally 303 SNPs associated with nutrients and serum lipids were selected from GWAS database,satisfying P<5×10^-8.In addition,the subjects were all from the same population,including 108 990Europeans.2.A total of 22.25 million SNPs related to Parkinson’s disease were extracted from UK Biobank.After population validation,303 SNPs related to Parkinson’s disease were screened out.3.Among the nutrients investigated by the paper,the results of MR-IVW Method showed that the increased serum concentration of vitamin B₁₂（OR=0.68;95%CI:0.52-0.89;adjusted P<0.0001）and docosahexaenoic acid（DHA）（OR=0.57;95%CI:0.40-0.82;adjusted P=0.0002）were associated with the lower risk of Parkinson’s disease.However,other nutrients included were found to be not associated with risk of Parkinson’s disease.4.In the assessment of serum lipids,the results showed that high-density lipoprotein（OR=1.19;95%CI:0.97-1.46;adjusted P=0.09）,low-density lipoprotein（OR=1.07;95%CI:0.88-1.30;adjusted P=0.498）,total cholesterol（OR=1.09;95%CI:0.90-1.32;adjusted P=0.361）and triglyceride（OR=1.14;95%CI:0.84-1.55;adjusted P=0.388）were not associated with risk of Parkinson’s disease.Conclusion:Through MR analysis,our findings provide new evidence for potential causality between vitamin B₁₂ and DHA and risk of Parkinson’s disease.Moreover,vitamin B₁₂ and DHA may be the protective factors of Parkinson’s disease.However,there is no association between serum lipids and risk of Parkinson’s disease,indicating that it may not be possible to reduce the risk of Parkinson’s disease by improving the level of lipids in the serum.Due to the limitations of MR analysis,a large number of randomized controlled trials are required to further verify the causal association between vitamin B₁₂ and DHA and risk of Parkinson’s disease.The purpose of this study is to provide evidence for epidemiological study and fundamental research to explore the risk factors of Parkinson’s disease.