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Review
. 2022 Jul 11:16:889802.
doi: 10.3389/fnins.2022.889802. eCollection 2022.

Genetic Elements at the Alpha-Synuclein Locus

Jordan Prahl  1 , Gerhard A Coetzee  1
Affiliations
Review

Genetic Elements at the Alpha-Synuclein Locus

Jordan Prahl et al. Front Neurosci. .

Abstract

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 SNCA 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 SNCA expression, calling into question the validity of assigning function to the nearest gene, SNCA. In this review, we examine additional genes and risk variants present at the SNCA locus and how they may contribute to Parkinson's disease. Using the SNCA locus as an example, we hope to demonstrate that deeper and detailed functional validations are required for high impact disease-linked variants.

Keywords: GWAS; Parkinson’s disease; alpha-synuclein (SNCA); neurodevelopment; rs356182.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

FIGURE 1
FIGURE 1
Genomic map of the SNCA locus. Selected gene positions displayed in blue. Gray lines denote relative single nucleotide polymorphism (SNP) positions.
See this image and copyright information in PMC

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