Genome and epigenome wide studies of neurological protein biomarkers in the Lothian Birth Cohort 1936
Year: 2019
Type: article
Study design: Observational Study
Abstract: Although plasma proteins may serve as markers of neurological disease risk, the molecular mechanisms responsible for inter-individual variation in plasma protein levels are poorly understood. Therefore, we conduct 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 healthy older adults). We identify 41 independent genome-wide significant (P < 5.4 × 10−10) loci for 33 proteins and 26 epigenome-wide significant (P < 3.9 × 10−10) sites associated with the levels of 9 proteins. Using this information, we identify biological pathways in which putative neurological biomarkers are implicated (neurological, immunological and extracellular matrix metabolic pathways). We also observe causal relationships (by Mendelian randomisation analysis) between changes in gene expression (DRAXIN, MDGA1 and KYNU), or DNA methylation profiles (MATN3, MDGA1 and NEP), and altered plasma protein levels. Together, this may help inform causal relationships between biomarkers and neurological diseases.
Source: Nature Communications
Language: English
Subfield: Genetics
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $5,200
Funders: Wellcome Trust, Age UK, University of Edinburgh, University of Queensland, Alzheimer’s Research UK, Centre for Cognitive Ageing and Cognitive Epidemiology, National Institutes of Health, Directorate for Biological Sciences, Medical Research Council, Biotechnology and Biological Sciences Research Council, Australian Research Council, National Health and Medical Research Council, National Institute on Aging, Eunice Kennedy Shriver National Institute of Child Health and Human Development
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., G2165108532, G2730595978, G2954243588, Phenotypic profiling from DNA using genetic and epigenetic information, G3229869697, Inheritance of DNA methylation, G3561803360, G3649208995, G3669141092, G3868569194, Complex trait genomics, Using genomics to understand psychiatric disorders, G3933842093, G3996179666, G4519464314, G4527525017, G4641403149, G483280169, G5026251150, G5067462658, G5139826593, G5490630913, G5834621717, G6223125567, Neurogenetics and Statistical Genomics, G6868616705, A genome-wide association study of non-pathological cognitive ageing, G718988473, Evaluating Longitudinal Changes in the Human Structural Connectome in Relation to Cognitive Aging, G7653015201, G7771854671, G829891318, CAGE: Consortium for the Architecture of Gene Expression, G9000063527, G9000159272
OpenAlex ID: W2960298137