Abstract: Alzheimer’s disease (AD) and Parkinson’s disease (PD) both manifest as a devastating age-related progressive neurodegeneration. At a basic level, neurodegenerative diseases such as AD and PD result from the wrong genes being expressed in the wrong ways at the wrong times. Moreover, these are diseases of age with most patients manifesting symptoms after age 60. This age-associated onset of symptoms indicates that in addition to the known genetic causes of neurodegeneration, there may also be epigenetic underpinnings to these diseases. This leads to the hypothesis that understanding the epigenome in AD and PD has the potential to provide key insights into the underlying molecular pathogenesis of neurodegeneration. The Corces lab is interested in how the genome and epigenome intersect and how inherited genetic variation interfaces with lived experiences and environmental factors to produce durable and functional epigenetic alterations that lead to disease. We combine multi-omic sequencing approaches and in vitro screening to identify cellular states or cell types associated with disease progression. This talk will focus on the genetic component of AD and PD, detailing our attempts to functionally annotate inherited noncoding polymorphisms using a combination of single-cell chromatin accessibility profiling, three-dimensional chromosome conformation capture, and a machine learning framework to provide vertical integration of this epigenomic data with sequence context.