Identification of JAZF1, KNOP1, and PLEKHA1 as causally associated genes and drug targets for Alzheimer's disease : a summary data-based Mendelian randomization study
Zhai, Yuhan ; Li, Ning ; Zhang, Yujie ; Li, Haibin ; Wu, Lijuan ; Wei, Cuibai ; Ji, Jianguang LU
and Zheng, Deqiang
LU
(2024)
In Inflammopharmacology
32(6).
p.3913-3923
- Abstract
BACKGROUND: There is a growing body of evidence indicating the significant role of the immune system and immune cells in the progression of Alzheimer's disease (AD). However, the exact role of genes from various immune cell types in AD remains unclear. We aimed to utilize summary data-based Mendelian randomization (SMR) to explore the potential causal relationships between genes in specific immune cells and the risk of AD.
METHODS: By utilizing data sets of expression quantitative trait loci (eQTL) for 14 different immune cell types and large-scale AD genome-wide association study (GWAS), we employed SMR to identify key genes associated with AD within specific immune cells. Sensitivity analyses, including F-statistic,... (More)
BACKGROUND: There is a growing body of evidence indicating the significant role of the immune system and immune cells in the progression of Alzheimer's disease (AD). However, the exact role of genes from various immune cell types in AD remains unclear. We aimed to utilize summary data-based Mendelian randomization (SMR) to explore the potential causal relationships between genes in specific immune cells and the risk of AD.
METHODS: By utilizing data sets of expression quantitative trait loci (eQTL) for 14 different immune cell types and large-scale AD genome-wide association study (GWAS), we employed SMR to identify key genes associated with AD within specific immune cells. Sensitivity analyses, including F-statistic, colocalization, and assessment of horizontal pleiotropy, were further conducted to validate the discovered genes. In addition, replication analyses were performed in AD GWAS from the FinnGen consortium. Finally, we further identified existing drugs that target or interact with the druggable genes and reviewed the studies about the associations between these drugs and AD.
RESULTS: SMR analysis revealed 342 genes associated with AD across 14 immune cell types. Further sensitivity analyses identified nine genes, CTSH, FCER1G, FNBP4, HLA-E, JAZF1, KNOP1, PLEKHA1, RP11-960L18.1, and ZNF638 that had significant associations with AD across nine specific immune cell types. JAZF1, KNOP1 and PLEKHA1 were replicated in an independent analysis using the GWAS data. The review on gene-related drugs also supported these findings.
CONCLUSIONS: Our research suggests that the expression of the genes JAZF1, KNOP1, and PLEKHA1 in specific immune cell types is related to the risk of AD.
(Less)
- author
- Zhai, Yuhan
; Li, Ning
; Zhang, Yujie
; Li, Haibin
; Wu, Lijuan
; Wei, Cuibai
; Ji, Jianguang
LU
and Zheng, Deqiang
LU
- organization
- publishing date
- 2024-10-25
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Inflammopharmacology
- volume
- 32
- issue
- 6
- pages
- 3913 - 3923
- publisher
- Springer
- external identifiers
-
- pmid:39455528
- scopus:85207338062
- ISSN
- 1568-5608
- DOI
- 10.1007/s10787-024-01583-z
- language
- English
- LU publication?
- yes
- additional info
- © 2024. The Author(s), under exclusive licence to Springer Nature Switzerland AG.
- id
- ce93bb98-9ecd-417b-9742-7ca760959584
- date added to LUP
- 2024-10-27 15:12:45
- date last changed
- 2025-07-15 03:35:57
@article{ce93bb98-9ecd-417b-9742-7ca760959584,
abstract = {{<p>BACKGROUND: There is a growing body of evidence indicating the significant role of the immune system and immune cells in the progression of Alzheimer's disease (AD). However, the exact role of genes from various immune cell types in AD remains unclear. We aimed to utilize summary data-based Mendelian randomization (SMR) to explore the potential causal relationships between genes in specific immune cells and the risk of AD.</p><p>METHODS: By utilizing data sets of expression quantitative trait loci (eQTL) for 14 different immune cell types and large-scale AD genome-wide association study (GWAS), we employed SMR to identify key genes associated with AD within specific immune cells. Sensitivity analyses, including F-statistic, colocalization, and assessment of horizontal pleiotropy, were further conducted to validate the discovered genes. In addition, replication analyses were performed in AD GWAS from the FinnGen consortium. Finally, we further identified existing drugs that target or interact with the druggable genes and reviewed the studies about the associations between these drugs and AD.</p><p>RESULTS: SMR analysis revealed 342 genes associated with AD across 14 immune cell types. Further sensitivity analyses identified nine genes, CTSH, FCER1G, FNBP4, HLA-E, JAZF1, KNOP1, PLEKHA1, RP11-960L18.1, and ZNF638 that had significant associations with AD across nine specific immune cell types. JAZF1, KNOP1 and PLEKHA1 were replicated in an independent analysis using the GWAS data. The review on gene-related drugs also supported these findings.</p><p>CONCLUSIONS: Our research suggests that the expression of the genes JAZF1, KNOP1, and PLEKHA1 in specific immune cell types is related to the risk of AD.</p>}},
author = {{Zhai, Yuhan and Li, Ning and Zhang, Yujie and Li, Haibin and Wu, Lijuan and Wei, Cuibai and Ji, Jianguang and Zheng, Deqiang}},
issn = {{1568-5608}},
language = {{eng}},
month = {{10}},
number = {{6}},
pages = {{3913--3923}},
publisher = {{Springer}},
series = {{Inflammopharmacology}},
title = {{Identification of JAZF1, KNOP1, and PLEKHA1 as causally associated genes and drug targets for Alzheimer's disease : a summary data-based Mendelian randomization study}},
url = {{http://dx.doi.org/10.1007/s10787-024-01583-z}},
doi = {{10.1007/s10787-024-01583-z}},
volume = {{32}},
year = {{2024}},
}