Genetic and epigenetic architectures of neurological protein biomarkers in the Lothian Birth Cohort 1936
Year: 2019
Type: preprint
Study design: Observational Study
Abstract: Although plasma proteins may serve as important markers of disease risk in neurological conditions, the molecular mechanisms responsible for inter-individual variation in plasma protein levels are poorly understood. In this study, we conducted genome- and epigenome-wide association studies on the levels of 92 neurological proteins to identify genetic and epigenetic loci associated with their plasma concentrations (n = 750). We identified 62 independent genome-wide significant loci for 37 proteins (P < 5.4 × 10 −10 ) and 68 epigenome-wide significant sites associated with the levels of 7 proteins (P < 3.9 × 10 −10 ). Using this information, we identified biological pathways in which putative neurological biomarkers are implicated as well as molecular mechanisms through which genetic variation may perturb plasma protein levels. Additionally, we found evidence that poliovirus receptor is causally associated with Alzheimer’s disease. In conclusion, we identified many novel genetic and epigenetic factors that are associated with neurological protein levels which may inform disease biology and establish causal relationships between biomarkers and neurological diseases.
DOI: 10.1101/558940
Language: English
Subfield: Genetics
Domain: Life Sciences
Open Access status: green
Funders: Wellcome Trust, Age UK, University of Edinburgh, University of Queensland, Centre for Cognitive Ageing and Cognitive Epidemiology, National Institutes of Health, Directorate for Biological Sciences, Medical Research Council, Australian Research Council, National Health and Medical Research Council
Awards: G1184531726, Centre for Cognitive Ageing & Cognitive Epidemiology, Genetics of DNA Methylation and Its Role in Disease Susecptibility, Translational Neuroscience - training the next generation of basic neuroscientists to embrace clinical research., G2113082864, G2730595978, Phenotypic profiling from DNA using genetic and epigenetic information, G3229869697, Inheritance of DNA methylation, G3561803360, G3669141092, G3868569194, Complex trait genomics, Using genomics to understand psychiatric disorders, G3933842093, G3996179666, G4519464314, G4527525017, G5067462658, G5139826593, G5490630913, G5834621717, G6223125567, Neurogenetics and Statistical Genomics, G6868616705, G718988473, G7653015201, G7771854671, G829891318, CAGE: Consortium for the Architecture of Gene Expression, G8733687393
OpenAlex ID: W4250002587