Table 1.
Top candidate risk SNPs that overlap active regulatory DNA
| SNP | Closest gene | GWAS p value | Function of gene | Role in neurodegeneration |
|---|---|---|---|---|
| rs12726330 | SLC50A1 (SWEET1) | 2.208x10−27 | glucose transport across the cell membrane45 | No studies have directly evaluated SLC50A1, but decreased expression of glucose transporters correlates with hypometabolism of glucose in neurodegenerative diseases.46 |
| rs2737004 | SNCA | 7.60x10−11 | regulation of dopamine release, induces fibrilization of microtubule-associated protein tau, and protection against apoptosis by inhibiting p53 and caspase-3 activation47 | It is mostly known to form toxic aggregates in neurons, but, in iPSC-derived macrophages from patients with an SNCA triplication, phagocytosis and cytokine release was impaired.48,49 |
| rs144814361 | BAG3 | 9.07x10−11 | co-chaperone that interacts with Hsp70 to prevent apoptosis during aging and under conditions of stress49 | The protein is protective against neurodegeneration by preventing NLRP3 activation and inflammation in microglia.50 |
| rs3813020 | FBXL19 | 2.05x10−10 | regulates the ubiquitination and degradation of inflammatory cytokines,51 regulates RhoA signaling52 |
Its role in neurodegeneration has not directly been tested. However, loss of RhoA is associated with microglia dysfunction and neurodegeneration.53 |
| rs4889599 | SETD1A | 7.34x10−10 | histone methyltransferase that regulates transcriptional programming during embryogenesis54 | Loss of function is associated with neurodevelopment disorders and dysfunctional neuronal metabolism.55 It is a GWAS-identified PD risk gene, but its functional involvement in the disease is unknown.56 |
| rs823114 rs7536483 |
NUCKS1 | 4.35x10−9 | involved in cell growth, proliferation, DNA repair, metabolism, and inflammatory and immune responses57 | The gene is part of the PARK16 locus (one of the first to be identified by PD GWAS). Its expression is downregulated in PD patients, but its causal mechanisms are unknown.58 |