Quantitative and causal analysis for inflammatory genes and the risk of Parkinson’s disease

BackgroundThe dysfunction of immune system and inflammation contribute to the Parkinson’s disease (PD) pathogenesis. Cytokines, oxidative stress, neurotoxin and metabolism associated enzymes participate in neuroinflammation in PD and the genes involved in them have been reported to be associated wit...

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Main Authors: Minhan Yi, Jiaxin Li, Shijie Jian, Binbin Li, Zini Huang, Li Shu, Yuan Zhang
Format: Article
Language:English
Published: Frontiers Media S.A. 2023-02-01
Series:Frontiers in Immunology
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fimmu.2023.1119315/full
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author Minhan Yi
Minhan Yi
Minhan Yi
Jiaxin Li
Jiaxin Li
Jiaxin Li
Shijie Jian
Binbin Li
Binbin Li
Zini Huang
Li Shu
Yuan Zhang
Yuan Zhang
author_facet Minhan Yi
Minhan Yi
Minhan Yi
Jiaxin Li
Jiaxin Li
Jiaxin Li
Shijie Jian
Binbin Li
Binbin Li
Zini Huang
Li Shu
Yuan Zhang
Yuan Zhang
author_sort Minhan Yi
collection DOAJ
description BackgroundThe dysfunction of immune system and inflammation contribute to the Parkinson’s disease (PD) pathogenesis. Cytokines, oxidative stress, neurotoxin and metabolism associated enzymes participate in neuroinflammation in PD and the genes involved in them have been reported to be associated with the risk of PD. In our study, we performed a quantitative and causal analysis of the relationship between inflammatory genes and PD risk.MethodsStandard process was performed for quantitative analysis. Allele model (AM) was used as primary outcome analysis and dominant model (DM) and recessive model (RM) were applied to do the secondary analysis. Then, for those genes significantly associated with the risk of PD, we used the published GWAS summary statistics for Mendelian Randomization (MR) to test the causal analysis between them.ResultsWe included 36 variants in 18 genes for final pooled analysis. As a result, IL-6 rs1800795, TNF-α rs1799964, PON1 rs854560, CYP2D6 rs3892097, HLA-DRB rs660895, BST1 rs11931532, CCDC62 rs12817488 polymorphisms were associated with the risk of PD statistically with the ORs ranged from 0.66 to 3.19 while variants in IL-1α, IL-1β, IL-10, MnSOD, NFE2L2, CYP2E1, NOS1, NAT2, ABCB1, HFE and MTHFR were not related to the risk of PD. Besides, we observed that increasing ADP-ribosyl cyclase (coded by BST1) had causal effect on higher PD risk (OR[95%CI] =1.16[1.10-1.22]) while PON1(coded by PON1) shown probably protective effect on PD risk (OR[95%CI] =0.81[0.66-0.99]).ConclusionSeveral polymorphisms from inflammatory genes of IL-6, TNF-α, PON1, CYP2D6, HLA-DRB, BST1, CCDC62 were statistically associated with the susceptibility of PD, and with evidence of causal relationships for ADP-ribosyl cyclase and PON1 on PD risk, which may help understand the mechanisms and pathways underlying PD pathogenesis.
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spelling doaj.art-58da8e559f894ef6b5d429035cb345b12023-02-28T06:18:14ZengFrontiers Media S.A.Frontiers in Immunology1664-32242023-02-011410.3389/fimmu.2023.11193151119315Quantitative and causal analysis for inflammatory genes and the risk of Parkinson’s diseaseMinhan Yi0Minhan Yi1Minhan Yi2Jiaxin Li3Jiaxin Li4Jiaxin Li5Shijie Jian6Binbin Li7Binbin Li8Zini Huang9Li Shu10Yuan Zhang11Yuan Zhang12Department of Respiratory Medicine, Xiangya Hospital, Central South University, Changsha, Hunan, ChinaSchool of Life Sciences, Central South University, Changsha, Hunan, ChinaNational Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan, ChinaDepartment of Respiratory Medicine, Xiangya Hospital, Central South University, Changsha, Hunan, ChinaNational Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan, ChinaXiangya School of Medicine, Central South University, Changsha, Hunan, ChinaSchool of Life Sciences, Central South University, Changsha, Hunan, ChinaDepartment of Respiratory Medicine, Xiangya Hospital, Central South University, Changsha, Hunan, ChinaXiangya School of Medicine, Central South University, Changsha, Hunan, ChinaBangor College, Central South University of Forestry and Technology, Changsha, Hunan, ChinaNational Health Commission Key Laboratory for Birth Defect Research and Prevention, Hunan Provincial Maternal and Child Health Care Hospital, Changsha, Hunan, ChinaDepartment of Respiratory Medicine, Xiangya Hospital, Central South University, Changsha, Hunan, ChinaNational Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan, ChinaBackgroundThe dysfunction of immune system and inflammation contribute to the Parkinson’s disease (PD) pathogenesis. Cytokines, oxidative stress, neurotoxin and metabolism associated enzymes participate in neuroinflammation in PD and the genes involved in them have been reported to be associated with the risk of PD. In our study, we performed a quantitative and causal analysis of the relationship between inflammatory genes and PD risk.MethodsStandard process was performed for quantitative analysis. Allele model (AM) was used as primary outcome analysis and dominant model (DM) and recessive model (RM) were applied to do the secondary analysis. Then, for those genes significantly associated with the risk of PD, we used the published GWAS summary statistics for Mendelian Randomization (MR) to test the causal analysis between them.ResultsWe included 36 variants in 18 genes for final pooled analysis. As a result, IL-6 rs1800795, TNF-α rs1799964, PON1 rs854560, CYP2D6 rs3892097, HLA-DRB rs660895, BST1 rs11931532, CCDC62 rs12817488 polymorphisms were associated with the risk of PD statistically with the ORs ranged from 0.66 to 3.19 while variants in IL-1α, IL-1β, IL-10, MnSOD, NFE2L2, CYP2E1, NOS1, NAT2, ABCB1, HFE and MTHFR were not related to the risk of PD. Besides, we observed that increasing ADP-ribosyl cyclase (coded by BST1) had causal effect on higher PD risk (OR[95%CI] =1.16[1.10-1.22]) while PON1(coded by PON1) shown probably protective effect on PD risk (OR[95%CI] =0.81[0.66-0.99]).ConclusionSeveral polymorphisms from inflammatory genes of IL-6, TNF-α, PON1, CYP2D6, HLA-DRB, BST1, CCDC62 were statistically associated with the susceptibility of PD, and with evidence of causal relationships for ADP-ribosyl cyclase and PON1 on PD risk, which may help understand the mechanisms and pathways underlying PD pathogenesis.https://www.frontiersin.org/articles/10.3389/fimmu.2023.1119315/fullinflammationParkinson’s diseasegeneticspolymorphismcausal analysis
spellingShingle Minhan Yi
Minhan Yi
Minhan Yi
Jiaxin Li
Jiaxin Li
Jiaxin Li
Shijie Jian
Binbin Li
Binbin Li
Zini Huang
Li Shu
Yuan Zhang
Yuan Zhang
Quantitative and causal analysis for inflammatory genes and the risk of Parkinson’s disease
Frontiers in Immunology
inflammation
Parkinson’s disease
genetics
polymorphism
causal analysis
title Quantitative and causal analysis for inflammatory genes and the risk of Parkinson’s disease
title_full Quantitative and causal analysis for inflammatory genes and the risk of Parkinson’s disease
title_fullStr Quantitative and causal analysis for inflammatory genes and the risk of Parkinson’s disease
title_full_unstemmed Quantitative and causal analysis for inflammatory genes and the risk of Parkinson’s disease
title_short Quantitative and causal analysis for inflammatory genes and the risk of Parkinson’s disease
title_sort quantitative and causal analysis for inflammatory genes and the risk of parkinson s disease
topic inflammation
Parkinson’s disease
genetics
polymorphism
causal analysis
url https://www.frontiersin.org/articles/10.3389/fimmu.2023.1119315/full
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