| Title: | Mapping the serum proteome to neurological diseases using whole genome sequencing |
| Journal: | Nature Communications |
| Published: | 2 Dec 2021 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/34857772/ |
| DOI: | https://doi.org/10.1038/s41467-021-27387-1 |
| URL: | https://www.nature.com/articles/s41467-021-27387-1.pdf |
| Citations: | 38 (27 in last 2 years) as of 8 Aug 2024 |
Publication 10750
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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.</p>
16 Authors
- 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
1 Application
| Application ID | Title |
|---|---|
| 10205 | Cardiometabolic trait genetics |
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