Genome and epigenome wide studies of neurological protein biomarkers in the Lothian Birth Cohort 1936.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 31320639.
- Also identified by DOI 10.1038/s41467-019-11177-x and PMC identifier 6639385.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
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<sup>-10</sup>) loci for 33 proteins and 26 epigenome-wide significant (P < 3.9 × 10<sup>-10</sup>) 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.
Medical subject headings
- Biomarkers
- Blood Proteins
- Nervous System Diseases