Mapping the serum proteome to neurological diseases using whole genome sequencing

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

Research output: Contribution to journalArticlepeer-review

Abstract / Description of output

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.

Original languageEnglish
Pages (from-to)7042
JournalNature Communications
Issue number1
Publication statusPublished - 2 Dec 2021


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