Epigenome-wide association study, meta-analysis and risk profiling of whole blood in Parkinson's disease
Lie, I. H.; Tan, M. M. X.; Andersen, M. S.; Toft, M.; Pihlstrom, L.
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An increasing body of evidence indicates altered DNA methylation in Parkinsons disease (PD), yet the reproducibility and utility of such methylation changes are largely unexplored. We conducted an epigenome-wide association study (EWAS) in whole blood, including 280 PD and 279 control participants from Oslo, Norway. In meta-analysis with data from the Parkinsons Progression Markers Initiative (PPMI) and a previously published whole blood PD EWAS (total N=3068) we confirm SLC7A11 hypermethylation and nominate a novel suggestive differentially methylated CpG near LPIN1. A joint multiscore risk profiling model incorporating polygenic risk and methylation-based estimates of epigenetic PD risk, smoking and leukocyte proportions differentiated patients from control participants with an area under the receiver-operator curve or 0.82 in the Oslo cohort and 0.65 in PPMI. Our results highlight the power of DNA methylation profiling to capture multiple aspects of disease risk, indicating a biomarker potential for precision medicine in neurodegenerative disorders.
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