Association analysis of SYT11, FGF20, GCH1 rare variants in Parkinson's disease

Pu, Jiali; Lin, Zhi‐Hao; Zheng, Ran; Yan, Yiqun; Xue, Nai‐Jia; Yin, Xinzhen; Zhang, Baorong

doi:10.1111/cns.13745

Cited by 4 publications

(1 citation statement)

References 14 publications

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“…The GCH1 gene belongs to a family of GTP cyclizing hydrolases known to be involved in the biosynthesis of BH 4 [ 112 ], a cofactor for tyrosine hydroxylase (TH), which is the rate-limiting enzyme for dopamine biosynthesis [ 113 ]. Thus, variants in the GCH1 gene may contribute to dopa-responsive dystonia [ 114 ]. Using high-throughput transcriptomics, the study observed significant correlations between PD-related genes and ferroptosis-related genes at the transcriptional level and protein–protein interactions, revealing 22 unique differentially expressed genes that may act as a link between ferroptosis and PD [ 115 ].…”

Section: Cellular Defense System For Ferroptosis In Pdmentioning

confidence: 99%

The Role of Cellular Defense Systems of Ferroptosis in Parkinson’s Disease and Alzheimer’s Disease

Chu,

Li,

Sun

et al. 2023

IJMS

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Parkinson’s disease (PD) and Alzheimer’s disease (AD) are the most common rapidly developing neurodegenerative diseases that lead to serious health and socio-economic consequences. Ferroptosis is a non-apoptotic form of cell death; there is growing evidence to support the notion that ferroptosis is involved in a variety of pathophysiological contexts, and there is increasing interest in the role of ferroptosis in PD and AD. Simultaneously, cells may have evolved four defense systems to counteract the toxic effects of ferroptosis occasioned by lipid peroxidation. This review, which focuses on the analysis of ferroptosis in the PD and AD context, outlines four cellular defense systems against ferroptosis and how each of them is involved in PD and AD.

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Section: Cellular Defense System For Ferroptosis In Pdmentioning

confidence: 99%

The Role of Cellular Defense Systems of Ferroptosis in Parkinson’s Disease and Alzheimer’s Disease

Chu,

Li,

Sun

et al. 2023

IJMS

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Large-scale rare variant burden testing in Parkinson's disease

Makarious

Lake

Pitz

et al. 2023

Brain

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Parkinson’s disease (PD) has a large heritable component and genome-wide association studies to date have identified over 90 loci with disease-associated common variants, providing deeper insights into the disease biology. However, there have not been large-scale rare variant analyses for PD. To address this gap, we investigated the rare genetic component of PD at minor allele frequencies <1%, using whole genome and whole exome sequencing data from 7,184 PD cases, 6,701 proxy-cases, and 51,650 healthy controls from the Accelerating Medicines Partnership Parkinson's disease (AMP-PD) initiative, the National Institutes of Health, the UK Biobank, and Genentech. We performed burden tests meta-analyses on small indels and single nucleotide protein-altering variants, prioritized based on their predicted functional impact. Our work identified several genes reaching exome-wide significance. Two of these genes, GBA1 and LRRK2, have variants that have been previously implicated as risk factors for PD, with some variants in LRRK2 resulting in monogenic forms of the disease. We identify potential novel risk associations for variants in B3GNT3, AUNIP, ADH5, TUBA1B, OR1G1, CAPN10, and TREML1, but were unable to replicate the observed associations in independent datasets. Of these, B3GNT3 and TREML1 could provide new evidence for the role of neuroinflammation in PD. To date, this is the largest analysis of rare genetic variants in PD.

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Large-scale Rare Variant Burden Testing in Parkinson’s Disease Identifies Novel Associations with Genes Involved in Neuro-inflammation

Makarious¹,

Lake

Pitz

et al. 2022

Preprint

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Parkinsons disease (PD) has a large heritable component and genome-wide association studies to date have identified over 90 variants associated with PD, providing deeper insights into the disease biology. However, there have not been large-scale rare variant analyses for PD. To address this gap, we investigated the rare genetic component of PD at minor allele frequencies <1%, using whole genome and whole exome sequencing data from 7,184 PD cases, 6,701 proxy-cases, and 51,650 healthy controls from the Accelerating Medicines Partnership Parkinson's disease (AMP-PD) initiative, the National Institutes of Health, the UK Biobank, and Genentech. We performed burden tests meta-analyses on protein-altering variants, prioritized based on their predicted functional impact. Our work identified several genes reaching exome-wide significance. While two of these genes, GBA and LRRK2, have been previously implicated as risk factors for PD, we identify potential novel associations for B3GNT3, AUNIP, ADH5, TUBA1B, OR1G1, CAPN10, and TREML1. Of these, B3GNT3 and TREML1 provide new evidence for the role of neuroinflammation in PD. To date, this is the largest analysis of rare genetic variation in PD.

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Association analysis of SYT11, FGF20, GCH1 rare variants in Parkinson's disease

Cited by 4 publications

References 14 publications

The Role of Cellular Defense Systems of Ferroptosis in Parkinson’s Disease and Alzheimer’s Disease

The Role of Cellular Defense Systems of Ferroptosis in Parkinson’s Disease and Alzheimer’s Disease

Large-scale rare variant burden testing in Parkinson's disease

Large-scale Rare Variant Burden Testing in Parkinson’s Disease Identifies Novel Associations with Genes Involved in Neuro-inflammation

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