Genome and epigenome wide studies of neurological protein biomarkers in the Lothian Birth Cohort 1936

Robert Hillary, Daniel L McCartney, Sarah Harris, Anna Stevenson, Anne Seeboth, Qian Zhang, David Liewald, Kathryn L. Evans, Craig Ritchie, Elliot M Tucker-Drob, Naomi R Wray, Allan F. Mcrae, Peter M. Visscher, Ian Deary, Riccardo E. Marioni

Research output: Contribution to journalArticlepeer-review

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.
Original languageEnglish
Article number3160
JournalNature Communications
Volume10
Early online date18 Jul 2019
DOIs
Publication statusPublished - Dec 2019

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