Population-Specific Differences in Pathogenic Variants of Genes Associated with Monogenic Parkinson’s Disease DOI Open Access
Victor Flores‐Ocampo, Wei Yin Lim, Natalia Ogonowski

et al.

Genes, Journal Year: 2025, Volume and Issue: 16(4), P. 454 - 454

Published: April 15, 2025

Background: Parkinson’s disease (PD) is a genetically complex neurodegenerative disorder. Up to 15% of cases are considered monogenic. However, research on monogenic PD has largely focused populations European ancestry, leaving gaps in our understanding genetic variability other populations. This study addresses this gap by analysing the allele frequencies pathogenic and likely variants known genes across eight global populations, using data from gnomAD database. Methods: We compiled list 27 associated with Mendelian Online Inheritance Man (OMIM) database, identified ClinVar. then performed pairwise comparisons included Variants significant frequency differences were further assessed silico pathogenicity predictions. Results: 81 17 statistically between at least two GBA1 most prevalent among PD-related genes, followed PLA2G6, ATP13A2, VPS13C, PRKN. exhibited greatest frequencies, particularly NM_000157.4:c.1226A>G (p.Asn409Ser) variant. Additionally, we observed population-specific variants, such as NM_032409.3:c.1040T>C (p.Leu347Pro) variant PINK1, which was East Asian Conclusions: Our findings reveal substantial linked PD, emphasising need for broader studies beyond These insights have important implications research, screening, pathogenesis diverse

Language: Английский

A PheWAS approach to identify associations of GBA1 variants with comprehensive phenotypes beyond neurological diseases DOI Creative Commons
Jia-Qi Yang,

Yuanfeng Huang,

Zheng Wang

et al.

npj Parkinson s Disease, Journal Year: 2025, Volume and Issue: 11(1)

Published: March 17, 2025

Given the established association between numerous GBA1 variants and specific neurological diseases, we extended exploration by a phenome-wide study to assess impact of on wider spectrum health-related traits. We identified 41 phenotypes associated with variants, 39 which were unreported, including 21 non-neurological 20 phenotypes. Based variant-level tests, found beyond particularly decreased gray-white matter contrast measures across 13 distinct brain regions, non-coding variant rs9628662 was six traits such as hypermetropia. Another rs3115534 showed associations eight biomarkers multiple categories, an increased risk benign digestive neoplasms. Notably, compared protein-coding p.T408M, had opposing effects three hematological biomarkers. Additionally, gene-level analyses revealed significant diseases Parkinson's disease. The findings demonstrated that significantly various

Language: Английский

Citations

0
Population-Specific Differences in Pathogenic Variants of Genes Associated with Monogenic Parkinson’s Disease DOI Open Access
Victor Flores‐Ocampo, Wei Yin Lim, Natalia Ogonowski

et al.

Genes, Journal Year: 2025, Volume and Issue: 16(4), P. 454 - 454

Published: April 15, 2025

Background: Parkinson’s disease (PD) is a genetically complex neurodegenerative disorder. Up to 15% of cases are considered monogenic. However, research on monogenic PD has largely focused populations European ancestry, leaving gaps in our understanding genetic variability other populations. This study addresses this gap by analysing the allele frequencies pathogenic and likely variants known genes across eight global populations, using data from gnomAD database. Methods: We compiled list 27 associated with Mendelian Online Inheritance Man (OMIM) database, identified ClinVar. then performed pairwise comparisons included Variants significant frequency differences were further assessed silico pathogenicity predictions. Results: 81 17 statistically between at least two GBA1 most prevalent among PD-related genes, followed PLA2G6, ATP13A2, VPS13C, PRKN. exhibited greatest frequencies, particularly NM_000157.4:c.1226A>G (p.Asn409Ser) variant. Additionally, we observed population-specific variants, such as NM_032409.3:c.1040T>C (p.Leu347Pro) variant PINK1, which was East Asian Conclusions: Our findings reveal substantial linked PD, emphasising need for broader studies beyond These insights have important implications research, screening, pathogenesis diverse

Language: Английский

Citations

0