AUTHOR=Prahl Jordan , Coetzee Gerhard A. 

TITLE=Genetic Elements at the Alpha-Synuclein Locus

JOURNAL=Frontiers in Neuroscience

VOLUME=16

YEAR=2022

URL=https://www.frontiersin.org/journals/neuroscience/articles/10.3389/fnins.2022.889802

DOI=10.3389/fnins.2022.889802

ISSN=1662-453X

ABSTRACT=<p>Genome-wide association studies have consistently shown that the alpha-synuclein locus is significantly associated with Parkinson’s disease. The mechanism by which this locus modulates the disease pathology and etiology remains largely under-investigated. This is due to the assumption that <italic>SNCA</italic> is the only driver of the functional aspects of several single nucleotide polymorphism (SNP) risk-signals at this locus. Recent evidence has shown that the risk associated with the top GWAS-identified variant within this locus is independent of <italic>SNCA</italic> expression, calling into question the validity of assigning function to the nearest gene, <italic>SNCA</italic>. In this review, we examine additional genes and risk variants present at the <italic>SNCA</italic> locus and how they may contribute to Parkinson’s disease. Using the <italic>SNCA</italic> locus as an example, we hope to demonstrate that deeper and detailed functional validations are required for high impact disease-linked variants.</p>