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Dysregulation of mitochondrial and proteolysosomal genes in Parkinson’s disease myeloid cells

Navarro, Elisa, Udine, Evan, Lopes, Katia de Paiva, Parks, Madison, Riboldi, Giulietta, Schilder, Brian M., Humphrey, Jack, Snijders, Gijsje J. L. +28 more·2021·Nature Aging
DOI 10.1038/s43587-021-00110-xPMC PMC8728893

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  • 11% of MiGA eQTL colocalizations could be reproduced in Young et al. data, and 15% of Young et al. colocalizations could be found in MiGA data, at PP4 > 0.5, whereas sharing between two monocyte datasets was 17-24%.

    “Overall, 11% of MiGA eQTL colocalizations could be reproduced in the Young et al. data, and 15% of the Young et al. colocalizations could be found in the MiGA data, at a relaxed PP4 > 0.5, whereas sharing between the two monocyte datasets41,42 was 17–24% with the same parameters (Supplementary Fig. 13).”

    From Genetic analysis of the human microglial transcriptome across brain regions, aging and disease pathologies (2022) · cites this paper as [42]

  • A large number of eQTLs in AD loci have shared effects between microglia and monocytes, for example MS4A6A, RABEP1, CD33, FCER1G, and ABCA7.

    “The comparison of m-values between microglia (MiGA) and monocytes (MyND42, and Fairfax41) showed that a large number of eQTLs in AD loci have shared effects between these two cell types, for example, MS4A6A, RABEP1, CD33, FCER1G, and ABCA7.”

    From Genetic analysis of the human microglial transcriptome across brain regions, aging and disease pathologies (2022) · cites this paper as [42]

  • No colocalization was observed in any other QTL dataset, though USP6NL is expressed five-fold higher in microglia than in monocytes.

    “No colocalization was observed in any other QTL dataset, though we note that USP6NL is expressed five-fold higher in microglia than in monocytes (MiGA median TPM = 15.77; MyND42 monocyte median TPM = 3.13).”

    From Genetic analysis of the human microglial transcriptome across brain regions, aging and disease pathologies (2022) · cites this paper as [42]

  • Our sample size is still small in comparison to monocyte and brain datasets.

    “First, our sample size is still small in comparison to monocyte and brain datasets22,41–43.”

    From Genetic analysis of the human microglial transcriptome across brain regions, aging and disease pathologies (2022) · cites this paper as [42]

  • Several methodological differences (recruitment of tissue, studied brain region, postmortem delay, pH, age, diagnosis, medication use) could interfere with the interpretation of comparisons between MiGA and other microglial datasets.

    “There are several methodological differences (recruitment of tissue, studied brain region, postmortem delay, pH, age, diagnosis, medication use) that could interfere with the interpretation of comparisons between MiGA and other microglial datasets5,9,42.”

    From Genetic analysis of the human microglial transcriptome across brain regions, aging and disease pathologies (2022) · cites this paper as [42]

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Authors
Navarro, E., Udine, E., Lopes, K. D. P., Parks, M., Riboldi, G., Schilder, B. M., Humphrey, J., Snijders, G. J. L., Vialle, R. A., Zhuang, M., Sikder, T., Argyrou, C., Allan, A., Chao, M. J., Farrell, K., Henderson, B., Simon, S., Raymond, D., Elango, S., Ortega, R. A., Shanker, V., Swan, M., Zhu, C. W., Ramdhani, R., Walker, R. H., Tse, W., Sano, M., Pereira, A. C., Ahfeldt, T., Goate, A. M., Bressman, S., Crary, J. F., de Witte, L., Frucht, S., Saunders-Pullman, R., & Raj, T.
ORCID
Venue
Nature Aging
Publisher
Springer Science and Business Media LLC
Published
2021-09-14
Volume
1
Issue
9
Pages
850-863
ISSN
2662-8465
DOI
10.1038/s43587-021-00110-x
PMC
PMC8728893
Cited by
48
References
16
Language
en
Licence
Funders
  • U.S. Department of Health & Human Services | NIH | National Institute of Neurological Disorders and Stroke (U01-NS107016, U01-NS094148, R01-NS116006)
  • U.S. Department of Health & Human Services | NIH | National Institute on Aging (R01-AG054005, R21-AG063130)

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