Causal role of myeloid cells in Parkinson's disease : Mendelian randomization study
© 2024. The Author(s), under exclusive licence to Springer Nature Switzerland AG..
BACKGROUND: Previous studies have observed elevated myeloid cells in the peripheral blood of patients with Parkinson's disease (PD), but the causal relationship between them remains to be elucidated. We investigated whether there is a causal relationship between different subtypes of peripheral blood myeloid cells and PD using Mendelian randomization (MR) combined with bioinformatics analysis. Exploring the etiology of PD from the perspective of genetics can remove confounding factors and provide a more reliable theoretical basis for elucidating the pathogenesis of PD.
METHODS: Comprehensive two-sample MR analysis and sensitivity analyses were conducted to explore the causal associations between 64 myeloid cell signatures and PD risk. The Venn diagram and protein-protein interaction network analysis of instrumental variables (IV) corresponding genes were used to further investigate the potential mechanism of myeloid cells influencing the pathogenesis of PD.
RESULTS: We investigated the impact of four immunophenotypes on the risk of PD, including Im MDSC% CD33dim HLA DR- CD66b- (relative count), CD33dim HLA DR+ CD11b+% CD33dim HLA DR+ (relative count), and CD11b on Mo MDSC (MFI) and CD11b on CD33br HLA DR+ CD14dim (MFI), while an immunophenotype's protective effect on PD was observed CD45 on Im MDSC (MFI). The results of bioinformatics analysis showed that CD33, NTRK2, PLD2, GRIK2 and RELN had protein interactions with the risk genes of PD.
CONCLUSIONS: Our study has demonstrated a close genetic correlation between different subtypes of myeloid cells and PD, providing guidance for early identification and immunotherapeutic development in patients with PD.
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2024 |
|---|---|
| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - year:2024 |
|---|---|
| Enthalten in: |
Inflammation research : official journal of the European Histamine Research Society ... [et al. - (2024) vom: 27. März |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Quan, Wei [VerfasserIn] |
|---|
| Links: |
|---|
| Themen: |
Causal inference |
|---|
| Anmerkungen: |
Date Revised 28.03.2024 published: Print-Electronic Citation Status Publisher |
|---|
| doi: |
10.1007/s00011-024-01867-8 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM370283023 |
|---|
| LEADER | 01000naa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM370283023 | ||
| 003 | DE-627 | ||
| 005 | 20240329001808.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 240329s2024 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1007/s00011-024-01867-8 |2 doi | |
| 028 | 5 | 2 | |a pubmed24n1353.xml |
| 035 | |a (DE-627)NLM370283023 | ||
| 035 | |a (NLM)38538756 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Quan, Wei |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Causal role of myeloid cells in Parkinson's disease |b Mendelian randomization study |
| 264 | 1 | |c 2024 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
| 338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Date Revised 28.03.2024 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status Publisher | ||
| 520 | |a © 2024. The Author(s), under exclusive licence to Springer Nature Switzerland AG. | ||
| 520 | |a BACKGROUND: Previous studies have observed elevated myeloid cells in the peripheral blood of patients with Parkinson's disease (PD), but the causal relationship between them remains to be elucidated. We investigated whether there is a causal relationship between different subtypes of peripheral blood myeloid cells and PD using Mendelian randomization (MR) combined with bioinformatics analysis. Exploring the etiology of PD from the perspective of genetics can remove confounding factors and provide a more reliable theoretical basis for elucidating the pathogenesis of PD | ||
| 520 | |a METHODS: Comprehensive two-sample MR analysis and sensitivity analyses were conducted to explore the causal associations between 64 myeloid cell signatures and PD risk. The Venn diagram and protein-protein interaction network analysis of instrumental variables (IV) corresponding genes were used to further investigate the potential mechanism of myeloid cells influencing the pathogenesis of PD | ||
| 520 | |a RESULTS: We investigated the impact of four immunophenotypes on the risk of PD, including Im MDSC% CD33dim HLA DR- CD66b- (relative count), CD33dim HLA DR+ CD11b+% CD33dim HLA DR+ (relative count), and CD11b on Mo MDSC (MFI) and CD11b on CD33br HLA DR+ CD14dim (MFI), while an immunophenotype's protective effect on PD was observed CD45 on Im MDSC (MFI). The results of bioinformatics analysis showed that CD33, NTRK2, PLD2, GRIK2 and RELN had protein interactions with the risk genes of PD | ||
| 520 | |a CONCLUSIONS: Our study has demonstrated a close genetic correlation between different subtypes of myeloid cells and PD, providing guidance for early identification and immunotherapeutic development in patients with PD | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Causal inference | |
| 650 | 4 | |a Mendelian randomization analysis | |
| 650 | 4 | |a Myeloid cells | |
| 650 | 4 | |a Parkinson’s disease | |
| 700 | 1 | |a Qin, Yidan |e verfasserin |4 aut | |
| 700 | 1 | |a Li, Jia |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Lin |e verfasserin |4 aut | |
| 700 | 1 | |a Song, Jia |e verfasserin |4 aut | |
| 700 | 1 | |a Xu, Jing |e verfasserin |4 aut | |
| 700 | 1 | |a Chen, Jiajun |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t Inflammation research : official journal of the European Histamine Research Society ... [et al. |d 1997 |g (2024) vom: 27. März |w (DE-627)NLM075208601 |x 1420-908X |7 nnns |
| 773 | 1 | 8 | |g year:2024 |g day:27 |g month:03 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.1007/s00011-024-01867-8 |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |j 2024 |b 27 |c 03 | ||