Year: 2021
Type: article
Study design: Observational Study
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.
Source: Nature Communications
Institutions: TUM Klinikum, Helmholtz Munich, Technical University of Munich, University of Edinburgh, Institute of Genetics and Cancer, MRC Human Genetics Unit, Fudan University, Karolinska Institutet, Greater Bay Area Institute of Precision Medicine, University of Cambridge, MRC Epidemiology Unit, Berlin Institute of Health at Charité - Universitätsmedizin Berlin, Charité – Universitätsmedizin Berlin, Harokopio University of Athens, Pfizer (United States)
Language: English
Subfield: Genetics
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $5,560
Awards: Aetiology of type 2 diabetes and related metabolic disorders, High Throughput Science - Investigating pathways to metabolic disease using "omic" approaches, G2892497062, G3812975344, G4839860845, Quantitative Traits in Health and Disease, G7211668644, Wellcome Trust Sanger Institute - generic account for deposition of all core- funded research papers
OpenAlex ID: W3217370940