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Png G, Barysenka A, Repetto L, et al. Mapping the serum proteome to neurological diseases using whole genome sequencing. Nat Commun. 2021;12(1):7042doi: 10.1038/s41467-021-27387-1.
Png, G., Barysenka, A., Repetto, L., Navarro, P., Shen, X., Pietzner, M., Wheeler, E., Wareham, N. J., Langenberg, C., Tsafantakis, E., Karaleftheri, M., Dedoussis, G., Mälarstig, A., Wilson, J. F., Gilly, A., & Zeggini, E. (2021). Mapping the serum proteome to neurological diseases using whole genome sequencing. Nature communications, 12(1), 7042. https://doi.org/10.1038/s41467-021-27387-1
Png, Grace, et al. "Mapping the serum proteome to neurological diseases using whole genome sequencing." Nature communications vol. 12,1 (2021): 7042. doi: https://doi.org/10.1038/s41467-021-27387-1
Png G, Barysenka A, Repetto L, Navarro P, Shen X, Pietzner M, Wheeler E, Wareham NJ, Langenberg C, Tsafantakis E, Karaleftheri M, Dedoussis G, Mälarstig A, Wilson JF, Gilly A, Zeggini E. Mapping the serum proteome to neurological diseases using whole genome sequencing. Nat Commun. 2021 Dec 02;12(1):7042. doi: 10.1038/s41467-021-27387-1. PMID: 34857772; PMCID: PMC8640022.
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Nat Commun. 2021 Dec 02;12(1):7042. doi: 10.1038/s41467-021-27387-1.

Mapping the serum proteome to neurological diseases using whole genome sequencing.

Nature communications

Grace Png, Andrei Barysenka, Linda Repetto, Pau Navarro, Xia Shen, Maik Pietzner, Eleanor Wheeler, Nicholas J Wareham, Claudia Langenberg, Emmanouil Tsafantakis, Maria Karaleftheri, George Dedoussis, Anders Mälarstig, James F Wilson, Arthur Gilly, Eleftheria Zeggini

Affiliations

  1. Institute of Translational Genomics, Helmholtz Zentrum München - German Research Center for Environmental Health, Neuherberg, Germany. [email protected].
  2. TUM School of Medicine, Technical University of Munich and Klinikum Rechts der Isar, Munich, Germany. [email protected].
  3. Institute of Translational Genomics, Helmholtz Zentrum München - German Research Center for Environmental Health, Neuherberg, Germany.
  4. Centre for Global Health Research, Usher Institute, University of Edinburgh, Edinburgh, UK.
  5. MRC Human Genetics Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, UK.
  6. Greater Bay Area Institute of Precision Medicine (Guangzhou), Fudan University, Guangzhou, China.
  7. Department of Medical Epidemiology and Biostatistics, Karolinska Institute, Stockholm, Sweden.
  8. MRC Epidemiology Unit, University of Cambridge, Cambridge, UK.
  9. Computational Medicine, Berlin Institute of Health (BIH), Charité University Medicine, Berlin, Germany.
  10. Anogia Medical Centre, Anogia, Greece.
  11. Echinos Medical Centre, Echinos, Greece.
  12. Department of Nutrition and Dietetics, School of Health Science and Education, Harokopio University of Athens, Athens, Greece.
  13. Department of Medicine, Karolinska Institute, Solna, Sweden.
  14. Emerging Science & Innovation, Pfizer Worldwide Research, Development and Medical, Cambridge, MA, USA.
  15. Institute of Translational Genomics, Helmholtz Zentrum München - German Research Center for Environmental Health, Neuherberg, Germany. [email protected].
  16. TUM School of Medicine, Technical University of Munich and Klinikum Rechts der Isar, Munich, Germany. [email protected].

PMID: 34857772 PMCID: PMC8640022 DOI: 10.1038/s41467-021-27387-1

Abstract

Despite the increasing global burden of neurological disorders, there is a lack of effective diagnostic and therapeutic biomarkers. Proteins are often dysregulated in disease and have a strong genetic component. Here, we carry out a protein quantitative trait locus analysis of 184 neurologically-relevant proteins, using whole genome sequencing data from two isolated population-based cohorts (N = 2893). In doing so, we elucidate the genetic landscape of the circulating proteome and its connection to neurological disorders. We detect 214 independently-associated variants for 107 proteins, the majority of which (76%) are cis-acting, including 114 variants that have not been previously identified. Using two-sample Mendelian randomisation, we identify causal associations between serum CD33 and Alzheimer's disease, GPNMB and Parkinson's disease, and MSR1 and schizophrenia, describing their clinical potential and highlighting drug repurposing opportunities.

© 2021. The Author(s).

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