Publications by authors named "Beisha Tang"
Limited whole genome sequencing (WGS) studies in Asian populations result in a lack of representative reference panels, thus hindering the discovery of ancestry-specific variants. Here, we present the South and East Asian reference Database (SEAD) panel ( https://imputationserver.westlake.
View Article and Find Full Text PDFBackground: Recent studies have reported that expanded GCA repeats in the GLS gene can cause glutaminase deficiency with ataxia phenotype. However, to data, no studies have investigated the distribution and role of GCA repeats in the GLS gene of Chinese individuals.
Objective: The aim was to investigate the distribution of GCA repeats in Chinese individuals, including undiagnosed ataxia patients for identifying causal factors, healthy controls for determining the normal range, and ATX-ATXN3 (spinocerebellar ataxia type 3, SCA3) patients for exploring genetic modifiers.
Article Synopsis
- - Glucosylceramidase beta 1 (GBA1) mutations increase the risk of Parkinson's disease (PD), but many carriers don't develop symptoms; this study explores factors that may influence PD development in GBA1 carriers.
- - The research used a database with participants divided into non-manifesting GBA1 carriers, controls, and those with GBA1-associated PD, analyzing exposure to pesticides, smoking, and other factors in relation to PD risk and symptoms.
- - Findings indicated that pesticide exposure was linked to a higher risk of PD in GBA1 carriers, while smoking seemed to lower that risk; however, early-stage GBA1-associated PD had more severe symptoms than non-manifesting carriers,
Article Synopsis
- Gain-of-function (GOF) variants enhance or change protein functions and are crucial for understanding diseases, but identifying them is tough due to scattered data and limited databases.
- The authors reviewed existing research to gather 3089 single-nucleotide variants and 72 small insertions/deletions across 579 genes linked to 1299 diseases, combining this with 3.5 million predicted GOF variants and employing a custom scoring system to rank their significance.
- They created GoFCards, a user-friendly database that allows geneticists and clinicians to easily access and analyze GOF variants, providing extensive annotations and the ability to prioritize variants even for those with limited bioinformatics experience.
Clinical features and progression of Parkinson's disease with LRRK2 variants: A prospective study.
Ann Clin Transl Neurol
November 2024
Objective: We established a prospective cohort study to investigate the differences in motor and non-motor symptoms between idiopathic Parkinson's disease (IPD) and Parkinson's disease in carriers of leucine-rich repeat kinase 2 (LRRK2) gene risk variants (LRRK2-PD).
Methods: The study included 1407 individuals with IPD and 649 individuals with LRRK2-PD (comprising 304 with LRRK2-G2385R, 220 with LRRK2-R1628P, and 105 with LRRK2-A419V). Differences in symptoms between LRRK2-PD and IPD were analyzed using LCMM modeling and Cox regression analysis.
Article Synopsis
- * This study investigated the effects of high-dose ganglioside GM1 on SCA3 patients by comparing it with low-dose GM1 and a placebo over 12 weeks, assessing changes in ataxia symptoms and safety.
- * Results showed that high-dose GM1 significantly improved motor function and daily living activities in patients, and all treatment groups were safe and well-tolerated.
Article Synopsis
- * The study involved whole-exome sequencing of 476 cases to discover candidate genes, leading to the identification of variants in the KCNJ10 gene, which were found in 3.07% of patients.
- * KCNJ10 variants were linked to milder PKD symptoms and impaired potassium channel function, impacting neuronal excitability and resulting in motor coordination issues in a mouse model, suggesting a possible genetic basis for PKD.
Article Synopsis
- Research highlights the genetic factors linked to schizophrenia (SCZ) through brain expression quantitative trait loci (eQTLs), primarily focusing on European populations, which limits insights into diverse populations.
- A comparative analysis across African Americans, Europeans, and East Asians revealed distinct eQTL patterns, with over 343,000 eQTLs unique to non-European groups, largely driven by differences in allele frequency.
- This study suggests that increasing diversity in genetic ancestry, rather than just sample size, can enhance understanding of SCZ's genetic basis and aid in identifying risk genes associated with the disorder.
Background: Parkinson's disease (PD) is a neurodegenerative disease caused by a combination of aging, environmental, and genetic factors. Previous research has implicated both causative and susceptibility genes in PD development. Nogo-A, a neurite outgrowth inhibitor, has been shown to impact axon growth through ligand-receptor interactions negatively, thereby involved in the deterioration of dopaminergic neurons.
View Article and Find Full Text PDFThe metabolomic profile of aging is complex. Here, we analyse 325 nuclear magnetic resonance (NMR) biomarkers from 250,341 UK Biobank participants, identifying 54 representative aging-related biomarkers associated with all-cause mortality. We conduct genome-wide association studies (GWAS) for these 325 biomarkers using whole-genome sequencing (WGS) data from 95,372 individuals and perform multivariable Mendelian randomization (MVMR) analyses, discovering 439 candidate "biomarker - disease" causal pairs at the nominal significance level.
View Article and Find Full Text PDFClinical, mechanistic, biomarker, and therapeutic advances in GBA1-associated Parkinson's disease.
Transl Neurodegener
September 2024
Parkinson's disease (PD) is the second most common neurodegenerative disease. The development of PD is closely linked to genetic and environmental factors, with GBA1 variants being the most common genetic risk. Mutations in the GBA1 gene lead to reduced activity of the coded enzyme, glucocerebrosidase, which mediates the development of PD by affecting lipid metabolism (especially sphingolipids), lysosomal autophagy, endoplasmic reticulum, as well as mitochondrial and other cellular functions.
View Article and Find Full Text PDFArticle Synopsis
- Frontotemporal dementia (FTD) is a complex disorder with various genetic and clinical expressions, and this study focused on a large cohort from China to better understand its characteristics.
- Out of 248 patients studied, nearly 20% had identifiable genetic mutations, with the C9orf72 dynamic mutation being the most common.
- Elevated levels of certain plasma biomarkers (GFAP, α-syn, NfL, and p-tau181) were found in FTD patients, indicating their potential for improving diagnostic accuracy.
Article Synopsis
- This study explores the role of structural variants, copy number variants, and short tandem repeats in Parkinson's disease by analyzing data from 466 PD patients and 513 controls.
- The researchers identified tens of thousands of genetic variations and found that certain CNV deletions were more common in PD patients, particularly at the ends of autosomal chromosomes.
- They confirmed specific deletions near the MUC19 and RXFP1 genes, along with certain repeat variants in SLC2A13, were significantly linked to PD and may affect the severity of other genetic risk factors like the LRRK2 G2385R variant.
There is an obvious clinical-pathological overlap between essential tremor and some known tremor-associated short tandem repeat expansion disorders. The aim is to analyse whether these short tandem repeat genes, including , , , , , , , , , , , , , and , are associated with familial essential tremor patients. Genetic analysis of repeat sizes in tremor-associated short tandem repeat expansions was performed in a large cohort of 515 familial essential tremor probands and 300 controls.
View Article and Find Full Text PDFThe characteristic and biomarker value of transcranial sonography in cerebellar ataxia.
Ann Clin Transl Neurol
August 2024
Objective: Transcranial sonography (TCS) is a noninvasive neuroimaging technique, visualizing deep brain structures and the ventricular system. Although widely employed in diagnosing various movement disorders, such as Parkinson's disease and dystonia, by detecting disease-specific abnormalities, the specific characteristics of the TCS in cerebellar ataxia remain inconclusive. We aimed to assess the potential value of TCS in patients with cerebellar ataxias for disease diagnosis and severity assessment.
View Article and Find Full Text PDFTo clarify the genetic role of phospholipase A2 (PLA2) genes in Parkinson's disease (PD), we performed a genetic association study in large Chinese population cohorts using next-generation sequencing. In this study, we analyzed both rare and common variants of 38 phospholipase A2 genes in two large cohorts. We detected 1558 and 1115 rare variants in these two cohorts, respectively.
View Article and Find Full Text PDFAssociation Analysis of Essential Tremor-Associated Genetic Variants in Sporadic Late-Onset Parkinson's Disease.
Tremor Other Hyperkinet Mov (N Y)
May 2024
Background: Parkinson's disease (PD) and Essential tremor (ET) are the two most common tremor diseases with recognized genetic pathogenesis. The overlapping clinical features suggest they may share genetic predispositions. Our previous study systematically investigated the association between rare coding variants in ET-associated genes and early-onset PD (EOPD), and found the suggestive association between () and EOPD.
View Article and Find Full Text PDFAutophagy is a conserved, catabolic process essential for maintaining cellular homeostasis. Malfunctional autophagy contributes to neurodevelopmental and neurodegenerative diseases. However, the exact role and targets of autophagy in human neurons remain elusive.
View Article and Find Full Text PDFArticle Synopsis
- A study analyzed the microbiota-gut-brain axis in 164 participants, comparing 83 nonagenarians (NAs) with 81 non-nonagenarians (NNAs) and their family members.
- Significant differences in 438 metabolites were found, with NAs showing higher levels of neuroactive compounds and anti-inflammatory substances.
- The results suggest that specific gut microbes and metabolites in NAs are linked to improved brain connectivity and cognitive preservation, highlighting the potential benefits of microbiome balance for longevity and cognitive health.
Background: An intronic GAA repeat expansion in FGF14 was recently identified as a cause of GAA-FGF14 ataxia. We aimed to characterise the frequency and phenotypic profile of GAA-FGF14 ataxia in a large Chinese ataxia cohort.
Methods: A total of 1216 patients that included 399 typical late-onset cerebellar ataxia (LOCA), 290 early-onset cerebellar ataxia (EOCA), and 527 multiple system atrophy with predominant cerebellar ataxia (MSA-c) were enrolled.
Article Synopsis
- Research on brain expression quantitative trait loci (eQTLs) has primarily focused on European populations, leaving gaps in understanding genetic risks for schizophrenia in diverse populations.
- A study analyzing data from African Americans, Europeans, and East Asians discovered that many eQTLs linked to schizophrenia risk are unique to non-European populations, highlighting significant differences due to allele frequency.
- The research identified new risk genes and regulatory variants that were overlooked in European studies, suggesting that increasing genetic diversity in research samples is crucial for better understanding schizophrenia's biological mechanisms and identifying additional risk factors.
Calcium-independent phospholipase Aβ (iPLAβ), a member of the phospholipase A2 (PLA2s) superfamily, is encoded by the PLA2G6 gene. Mutations in the PLA2G6 gene have been identified as the primary cause of infantile neuroaxonal dystrophy (INAD) and, less commonly, as a contributor to Parkinson's disease (PD). Recent studies have revealed that iPLAβ deficiency leads to neuroinflammation, iron accumulation, mitochondrial dysfunction, lipid dysregulation, and other pathological changes, forming a complex pathogenic network.
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- Paroxysmal kinesigenic dyskinesia (PKD) is linked to irregularities in brain circuit activities, and this study aims to identify its neurophysiological markers using high-density electroencephalogram (hd-EEG) signals.
- The research found that patients with PKD exhibit increased theta oscillations in various brain areas, which return to normal during remission, while non-remission patients show decreased functional connectivity in higher gamma frequency ranges.
- The study successfully developed predictive models to identify remission states in PKD patients and highlighted the potential of hd-EEG as a clinical tool for monitoring and diagnosing the disorder.