Manu Sharma
A5046131652- Parkinson's Disease Mechanisms and Treatments
- Neurological diseases and metabolism
- RNA regulation and disease
- Genetic Associations and Epidemiology
- Lysosomal Storage Disorders Research
- Nuclear Receptors and Signaling
- Neurological disorders and treatments
- Autism Spectrum Disorder Research
- Genomic variations and chromosomal abnormalities
- Mitochondrial Function and Pathology
- Genetic Neurodegenerative Diseases
- Cellular transport and secretion
- Genetics and Neurodevelopmental Disorders
- CRISPR and Genetic Engineering
- Amyotrophic Lateral Sclerosis Research
- Genomics and Rare Diseases
- Private Equity and Venture Capital
- Autophagy in Disease and Therapy
- Bioinformatics and Genomic Networks
- Botulinum Toxin and Related Neurological Disorders
- Endoplasmic Reticulum Stress and Disease
- Genomics and Chromatin Dynamics
- T-cell and B-cell Immunology
- Banana Cultivation and Research
- Cancer-related gene regulation
University of Tübingen
2015-2024
Weill Cornell Medicine
2023-2024
Cornell University
2023-2024
Inserm
2011-2024
MIND Research Institute
2024
Université de Versailles Saint-Quentin-en-Yvelines
2024
Centre de recherche en Epidémiologie et Santé des Populations
2024
Center for Human Genetics
2024
Université Paris-Saclay
2024
Hertie Institute for Clinical Brain Research
2013-2023
Recent studies indicate an increased frequency of mutations in the gene encoding glucocerebrosidase (GBA), a deficiency which causes Gaucher's disease, among patients with Parkinson's disease. We aimed to ascertain GBA ethnically diverse group disease.Sixteen centers participated our international, collaborative study: five from Americas, six Europe, two Israel, and three Asia. Each center genotyped standard DNA panel permit comparison genotyping results across centers. Genotypes phenotypic...
Significance Understanding loci nominated by genome-wide association studies (GWASs) is challenging. Here, we show, using the specific example of Parkinson disease, that identification protein–protein interactions can help determine most likely candidate for several GWAS loci. This result illustrates a significant general principle will apply across multiple diseases.
Abstract Background Increasing evidence supports an extensive and complex genetic contribution to PD. Previous genome‐wide association studies (GWAS) have shed light on the basis of risk for this disease. However, determinants PD age at onset are largely unknown. Objectives To identify onset. Methods Using data 28,568 cases, we performed a study based Results We estimated that heritability attributed common variation was ∼0.11, lower than overall (∼0.27), likely, in part, because subjective...
Recent genome-wide association studies (GWAS) and pathway analyses supported long-standing observations of an between immune-mediated diseases Parkinson disease (PD). The post-GWAS era provides opportunity for cross-phenotype different complex phenotypes.To test the hypothesis that there are common genetic risk variants conveying both PD autoimmune (ie, pleiotropy) to identify new shared their pathways by applying a novel statistical framework in approach.Using conjunction false discovery...
Abstract To test whether the synucleinopathies Parkinson's disease and multiple system atrophy (MSA) share a common genetic etiology, we performed candidate single nucleotide polymorphism (SNP) association study of 384 most associated SNPs in genome‐wide 413 MSA cases 3,974 control subjects. The 10 significant were then replicated additional 108 537 controls. at SNCA locus significantly with risk for increased development (combined p = 5.5 × 12 ; odds ratio 6.2). Ann Neurol 2009;65:610–614
Parkinson's disease is a genetically complex disorder. Multiple genes have been shown to contribute the risk of disease, and currently 90 independent variants identified by genome-wide association studies. Thus far, number (including SNCA, LRRK2, GBA) contain variability across spectrum frequency effect, from rare, highly penetrant common alleles with small effect sizes. Variants in GBA, encoding enzyme glucocerebrosidase, are associated Lewy body diseases such as dementia. These variants,...
<h3>Importance</h3> Substantial genome-wide association study (GWAS) work in Parkinson disease (PD) has led to the discovery of an increasing number loci shown reliably be associated with increased risk disease. Improved understanding underlying genes and mechanisms at these will key pathogenesis PD. <h3>Objective</h3> To investigate what genomic processes underlie sporadic <h3>Design Setting</h3> This genetic used bioinformatic tools Coloc transcriptome-wide (TWAS) integrate PD case-control...
Parkinson's disease is a neurodegenerative movement disorder that currently has no disease-modifying treatment, partly owing to inefficiencies in drug target identification and validation. We use Mendelian randomization investigate over 3,000 genes encode druggable proteins predict their efficacy as targets for disease. expression protein quantitative trait loci mimic exposure medications, we examine the causal effect on risk (in two large cohorts), age at onset progression. propose 23...
Parkinson's disease is a progressive neurodegenerative disorder with multifactorial causes, among which genetic risk factors play part. The RAB GTPases are regulators and substrates of LRRK2, variants in the LRRK2 gene important for disease. We aimed to explore variability within cases familial
Mutations in the parkin gene are most common cause of recessive familial Parkinson disease (PD). Parkin has been initially characterized as an ubiquitin E3 ligase, but pathological relevance this activity remains uncertain. Recently, impressive amount evidence accumulated that is involved maintenance mitochondrial function and biogenesis. We used a human neuroblastoma cell line model to study influence endogenous on genomic integrity. Using unbiased chromatin immunoprecipitation approach, we...
The mitochondrial chaperone mortalin has been linked to neurodegeneration in Parkinson's disease (PD) based on reduced protein levels affected brain regions of PD patients and its interaction with the PD-associated DJ-1. Recently, two amino acid exchanges ATPase domain (R126W) substrate-binding (P509S) were identified Spanish patients. Here, we a separate novel variant (A476T) German To define potential role as susceptibility factor PD, characterized functions all three variants different...
Eleven genetic loci have reached genome-wide significance in a recent meta-analysis of association studies Parkinson disease (PD) based on populations Caucasian descent. The extent to which these effects are consistent across different is unknown.Investigators from the Genetic Epidemiology Parkinson's Disease Consortium were invited participate study. A total 11 SNPs genotyped 8,750 cases and 8,955 controls. Fixed as well random models used provide summary risk estimates for variants. We...
Abstract We performed the largest genome-wide association study of PD to date, involving analysis 7.8M SNPs in 37.7K cases, 18.6K UK Biobank proxy-cases, and 1.4M controls. identified 90 independent significant signals across 78 loci, including 38 risk 37 novel loci. These variants explained 26-36% heritable PD. Tests causality within a Mendelian randomization framework putatively causal genes for 70 signals. Tissue expression enrichment suggested that signatures loci were heavily...