Mapping the serum proteome to neurological diseases using whole genome sequencing.
dc.contributor.author | Png, Grace | |
dc.contributor.author | Barysenka, Andrei | |
dc.contributor.author | Repetto, Linda | |
dc.contributor.author | Navarro, Pau | |
dc.contributor.author | Shen, Xia | |
dc.contributor.author | Pietzner, Maik | |
dc.contributor.author | Wheeler, Eleanor | |
dc.contributor.author | Wareham, Nicholas | |
dc.contributor.author | Langenberg, Claudia | |
dc.contributor.author | Tsafantakis, Emmanouil | |
dc.contributor.author | Karaleftheri, Maria | |
dc.contributor.author | Dedoussis, George | |
dc.contributor.author | Mälarstig, Anders | |
dc.contributor.author | Wilson, James F | |
dc.contributor.author | Gilly, Arthur | |
dc.contributor.author | Zeggini, Eleftheria | |
dc.date.accessioned | 2021-12-14T00:30:44Z | |
dc.date.available | 2021-12-14T00:30:44Z | |
dc.date.issued | 2021-12-02 | |
dc.identifier.issn | 2041-1723 | |
dc.identifier.uri | https://www.repository.cam.ac.uk/handle/1810/331372 | |
dc.description.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. | |
dc.publisher | Springer Science and Business Media LLC | |
dc.rights | Attribution 4.0 International | |
dc.rights.uri | https://creativecommons.org/licenses/by/4.0/ | |
dc.title | Mapping the serum proteome to neurological diseases using whole genome sequencing. | |
dc.type | Article | |
dc.publisher.department | Mrc Epidemiology Unit | |
dc.publisher.department | office of The School of Clinical Medicine | |
dc.date.updated | 2021-12-10T11:19:29Z | |
prism.issueIdentifier | 1 | |
prism.number | 7042 | |
prism.publicationDate | 2021 | |
prism.publicationName | Nat Commun | |
prism.startingPage | 7042 | |
prism.volume | 12 | |
dc.identifier.doi | 10.17863/CAM.78823 | |
dcterms.dateAccepted | 2021-11-11 | |
rioxxterms.versionofrecord | 10.1038/s41467-021-27387-1 | |
rioxxterms.version | VoR | |
dc.contributor.orcid | Png, Grace [0000-0003-3962-7436] | |
dc.contributor.orcid | Navarro, Pau [0000-0001-5576-8584] | |
dc.contributor.orcid | Shen, Xia [0000-0003-4390-1979] | |
dc.contributor.orcid | Pietzner, Maik [0000-0003-3437-9963] | |
dc.contributor.orcid | Wheeler, Eleanor [0000-0002-8616-6444] | |
dc.contributor.orcid | Wareham, Nicholas [0000-0003-1422-2993] | |
dc.contributor.orcid | Langenberg, Claudia [0000-0002-5017-7344] | |
dc.contributor.orcid | Mälarstig, Anders [0000-0003-2608-1358] | |
dc.contributor.orcid | Wilson, James F [0000-0001-5751-9178] | |
dc.contributor.orcid | Zeggini, Eleftheria [0000-0003-4238-659X] | |
dc.identifier.eissn | 2041-1723 | |
rioxxterms.type | Journal Article/Review | |
pubs.funder-project-id | Medical Research Council (MC_UU_12015/1) | |
pubs.funder-project-id | MRC (MC_PC_13046) | |
cam.issuedOnline | 2021-12-02 | |
cam.depositDate | 2021-12-10 | |
pubs.licence-identifier | apollo-deposit-licence-2-1 | |
pubs.licence-display-name | Apollo Repository Deposit Licence Agreement |
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