• In the past, genome-wide association studies (GWAS) have identified an important number of risk loci associated with AD pathology 3 , but a causal relationship remains difficult to establish. (nature.com)
  • Based on the "common disease-common variants hypothesis", genome-wide association studies (GWAS) have been extensively conducted to identify disease-susceptible genes. (jnss.org)
  • Although GWAS have successfully revealed numerous susceptibility genes for neurological diseases, odds ratios associated with these risk alleles are generally low and account for only a small portion of estimated heritability. (jnss.org)
  • Since the power of detection of rare alleles by GWAS employing common SNPs is limited, comprehensive genome sequencing is required to identify these rare variants. (jnss.org)
  • 2012). We have also contributed to genome-wide association studies (GWAS) seeking novel susceptibility loci for AD neuropathologic traits, including amyloid neuritic plaques and Tau neurofibrillary tangles. (bcm.edu)
  • Given that many studies demonstrated the high heritability of AD, ranging from 60 to 80%, researchers have performed targeted genetic studies or genome-wide association studies (GWAS) to link genetic variants such as single nucleotide polymorphisms (SNPs) to clinical outcomes [ 1 ]. (biomedcentral.com)
  • In the past 2 decades, genome-wide association studies (GWAS) have identifyed genetic susceptibility loci that confer the risk for sporadic PD [ 3 ]. (biomedcentral.com)
  • Genome-wide association studies (GWAS) and large-scale replication studies have identified common variants in 79 loci associated with breast cancer, explaining ∼14% of the familial risk of the disease. (ox.ac.uk)
  • To identify new susceptibility loci, we performed a meta-analysis of 11 GWAS, comprising 15,748 breast cancer cases and 18,084 controls together with 46,785 cases and 42,892 controls from 41 studies genotyped on a 211,155-marker custom array (iCOGS). (ox.ac.uk)
  • AD susceptibility has an established genetic basis which has been the focus of a large number of genome-wide association studies (GWAS) published over the last decade. (uni-luebeck.de)
  • Specifically, we utilized genotype and phenotype data from n = 931 individuals collected under the auspices of the European Medical Information Framework for Alzheimer's Disease Multimodal Biomarker Discovery (EMIF-AD MBD) study to perform a total of 19 separate GWAS analyses. (uni-luebeck.de)
  • Our GWAS analyses revealed several genome-wide significant associations for the neuropsychological performance measures, in particular those assayed longitudinally. (uni-luebeck.de)
  • In summary, our study highlights the power of using quantitative endophenotypes as outcome traits in AD-related GWAS analyses and nominates several new loci not previously implicated in cognitive decline. (uni-luebeck.de)
  • To identify additional RCC common susceptibility loci, we conducted an independent genome-wide association study (GWAS). (ox.ac.uk)
  • Although there has been much success in identifying genetic variants associated with common diseases using genome-wide association studies (GWAS), it has been difficult to demonstrate which variants are causal and what role they have in disease. (researchgate.net)
  • Here we have investigated a single nucleotide polymorphism (SNP) in the TNFRSF1A gene, that encodes tumour necrosis factor receptor 1 (TNFR1), which was discovered through GWAS to be associated with multiple sclerosis (MS), but not with other autoimmune conditions such as rheumatoid arthritis, psoriasis and Crohn's disease. (researchgate.net)
  • By analysing MS GWAS data in conjunction with the 1000 Genomes Project data we provide genetic evidence that strongly implicates this SNP, rs1800693, as the causal variant in the TNFRSF1A region. (researchgate.net)
  • Hence, our study demonstrates that clinical practice can be informed by comparing GWAS across common autoimmune diseases and by investigating the functional consequences of the disease-associated genetic variation. (researchgate.net)
  • Multiple genome-wide association studies (GWAS) over the past 10 years have uncovered more than 200 loci that independently contribute to disease pathogenesis. (researchgate.net)
  • To identify genetic variants underlying such differences and associated disease phenotypes, multinational consortia such as ENIGMA have used large magnetic resonance imaging (MRI) data sets in human GWAS studies. (biomedcentral.com)
  • Prior efforts to identify genetic variants underlying differences in brain structure have used large data sets in human genome-wide association studies (GWAS) or extensive mapping populations in mouse model systems. (biomedcentral.com)
  • Recent advances in genome-wide associate stories (GWAS) have enabled the identification of several genetic loci that collectively contribute to PD risk. (amp-pd.org)
  • This value is calculated by comparing individual-level genotype and phenotype data to a larger collection of weighted alleles from genome-wide association study summary (GWAS) statistics and this value indicates an individual's susceptibility based on alleles present in their genome. (amp-pd.org)
  • Genome-wide association studies (GWAS) have identified many genetic susceptibility loci for colorectal cancer (CRC). (wineinformationcouncil.eu)
  • Genome-wide studies of gene-environment interactions may identify variants that are not detected in GWAS of marginal gene effects. (wineinformationcouncil.eu)
  • DNA methylation map of mouse and human brain identifies target genes in Alzheimer's disease. (nature.com)
  • Advances in genomic technologies and statistical methods have converged to allow the discovery of susceptibility loci for complex genetic traits, and the field now confronts the enormous challenge to confirm the responsible genes and define their functions in the biology of health and disease. (bcm.edu)
  • In addition to the potential for fundamental biological insights, functional dissection of susceptibility genes will be essential to realize the full promise of human genetics for clinical applications. (bcm.edu)
  • Most notably, rare pathogenic mutations have been identified in the amyloid precursor protein, microtubule associate protein tau, and alpha-synuclein genes, encoding the primary constituents of the defining disease pathologies (amyloid plaques and Tau neurofibrillary tangles in AD, and Lewy bodies in PD, respectively). (bcm.edu)
  • Targeted genetic analyses, genome-wide association studies, and imaging genetic analyses have been performed to detect AD risk and protective genes and have successfully identified dozens of AD susceptibility loci. (biomedcentral.com)
  • We have proposed a novel disease-related brain transcriptomic mapping method to identify genes whose expression profiles spatially correlated with regional diagnostic effects on a studied brain trait. (biomedcentral.com)
  • Identifying and studying genes that contribute to Alzheimer s disease (AD) development will help us to understand the causes of AD, providing the basis for developing new treatments. (neurodegenerationresearch.eu)
  • Common variation in nine novel genes are known to increase susceptibility to AD. (neurodegenerationresearch.eu)
  • Dr. Wilhelmsen's laboratory is engaged in the genetic mapping of susceptibility loci for complex traits such as addiction and the positional cloning of genes responsible for neurodegenerative disorders. (unc.edu)
  • At UCSF, he established a clinical and laboratory program to identify addiction susceptibility genes. (unc.edu)
  • There are few conditions where there is a genetic susceptibility that shows more complex interactions between genes and the environment than addiction. (unc.edu)
  • Genetic variants of SNCA and LRRK2 genes are associated with sporadic PD susceptibility: a replication study in a Taiwanese cohort. (cdc.gov)
  • Analysis of 50 Neurodegenerative Genes in Clinically Diagnosed Early-Onset Alzheimer's Disease. (cdc.gov)
  • The critical next step will be to definitively identify the responsible genes and understand their functions in both health and disease. (texaschildrens.org)
  • Despite the promise of current human genetic methods, such as genome-wide association studies, they often fail to identify disease susceptibility genes with certainty, instead highlighting broad genomic regions. (texaschildrens.org)
  • We are taking advantage of the rapid and powerful genetics available in the fruit fly Drosophila melanogaster in order to accelerate the validation of responsible genes and an understanding of their functions in disease pathogenesis. (texaschildrens.org)
  • We are testing candidate human susceptibility genes for functional genetic interactions in these fly models of neurodegeneration. (texaschildrens.org)
  • This identified approximately 140 chromosome loci where nucleotides deviated from the reference sequence GRCh37 hg19 comprising the three genes TRPV1, LTB4R and LTB4R2. (researchgate.net)
  • By investigating SNP profiles associated with a disease trait, researchers would be able to reveal relevant genes. (biomedcentral.com)
  • Researchers hypothesize that many common diseases in humans are not caused by one genetic variation within a single gene, but are determined by complex interactions among multiple genes. (biomedcentral.com)
  • Then, it will just be a matter of time before physicians can screen individuals for susceptibility to a disease by analyzing their DNA samples for specific SNP patterns, and further design some experiments to target the genes that implicate the disease. (biomedcentral.com)
  • Nature Genetics) of the first new susceptibility genes for 17 years defined a pivotal moment in Alzheimer's genetics research. (cardiff.ac.uk)
  • What is striking about her group's findings is that the genes identified show patterns of relationship, which implicate novel disease mechanisms, including immunity, endocytosis, lipid transport and ubiquination. (cardiff.ac.uk)
  • We examined whether a genetic burden of variants in other lysosomal storage disorder genes is more broadly associated with Parkinson's disease susceptibility. (amsterdamumc.org)
  • The sequence kernel association test was used to interrogate variant burden among 54 lysosomal storage disorder genes, leveraging whole exome sequencing data from 1156 Parkinson's disease cases and 1679 control subjects. (amsterdamumc.org)
  • In secondary analyses designed to highlight the specific genes driving the aggregate signal, we confirmed associations at the GBA and SMPD1 loci and newly implicate CTSD, SLC17A5, and ASAH1 as candidate Parkinson's disease susceptibility genes. (amsterdamumc.org)
  • Quantitative Trait Loci and Candidate Genes for Neutrophil Recruitment in Sterile Inflammation Mapped in AXB-BXA Recombinant Inbred Mice. (genenetwork.org)
  • Genome-wide association analyses on large patient cohorts are generating large sets of candidate disease genes. (biomedcentral.com)
  • Supplementation with CoQ10 may be helpful in treating MSA, particularly for those with susceptibility-conferring COQ2 variants. (jnss.org)
  • In the coming years, with the completion of the largest possible genetic meta-analyses along with the advent of whole-genome sequencing, our knowledge of common and rare susceptibility variants will rapidly expand, implicating vast genetic networks including hundreds of loci in neurologic diseases. (bcm.edu)
  • The clinical manifestation of neurodegenerative disease is the culmination of a multi-tiered pathogenic cascade that evolves over decades-understanding how genetic variants impact this causal chain is essential. (bcm.edu)
  • Substantial evidence supports a model in which many genetic variants promote the development of neuropathology, subsequently leading to the clinical manifestations of disease. (bcm.edu)
  • However, these variants only account for roughly 32% of the genetic aetiology of the disease. (neurodegenerationresearch.eu)
  • It will utilise a novel exome chip, designed using 12,000 exome sequences and the 1000 genomes project, to assay 300,000 genetic variants. (neurodegenerationresearch.eu)
  • This paper provides a brief presentation on the genetics of multiple sclerosis susceptibility and on current work that uncovers the cellular effects, immunological and non-immunological, associated with genetic risk variants. (researchgate.net)
  • Moreover, the modest contribution that these variants make to disease risk has raised questions regarding their medical relevance. (researchgate.net)
  • As with many other complex diseases, risk of developing MS is driven by multiple common variants whose biological effects are not immediately clear. (researchgate.net)
  • A human microglia-like cellular model for assessing the effects of neurodegenerative disease gene variants. (cdc.gov)
  • A polygenic risk score (PRS) is used to evaluate one's overall risk or predisposition to a disease, taking into account an individual's genetic architecture that includes the effects of both protective and risk genetic variants. (amp-pd.org)
  • This allows comparison of different risk groups or potential mechanistic subtypes to better understand heterogeneity of disease and the role of specific genetic variants in the clinical features of patients and controls. (amp-pd.org)
  • Concretely, genome-wide association studies have detected numerous asthma-associated gene variants, while few of them (less than 10%) can be explained to contribute to the risk of asthma [ 10 ]. (researchsquare.com)
  • NeuroChip, an updated version of the NeuroX genotyping platform to rapidly screen for variants associated with neurological diseases. (texaschildrens.org)
  • We discovered a significant burden of rare, likely damaging lysosomal storage disorder gene variants in association with Parkinson's disease risk. (amsterdamumc.org)
  • However, variants in these loci explain only a small proportion of familial aggregation, and there are likely additional variants that are associated with CRC susceptibility. (wineinformationcouncil.eu)
  • To study this, we conducted a genome-wide analysis for interaction between genetic variants and alcohol consumption and cigarette smoking using data from the Colon Cancer Family Registry (CCFR) and the Genetics and Epidemiology of Colorectal Cancer Consortium (GECCO). (wineinformationcouncil.eu)
  • If replicated our suggestive finding of a genome-wide significant interaction between genetic variants and alcohol consumption might contribute to understanding colorectal cancer etiology and identifying subpopulations with differential susceptibility to the effect of alcohol on CRC risk. (wineinformationcouncil.eu)
  • Mutations are associated with mitochondrial dysfunction, leading to neuronal death in Parkinson's disease and aberrant metabolism in tumourigenesis. (wikipedia.org)
  • citation needed] Mutations in this gene are known to cause a familial form of Parkinson's disease known as autosomal recessive juvenile Parkinson's disease (AR-JP). (wikipedia.org)
  • Homozygosity for the more common haplotype H1 is associated with an increased risk for several tauopathies, but also for the synucleinopathy Parkinson's disease (PD). (biomedcentral.com)
  • Parkinson's disease (PD) is the second most common neurodegenerative disease after Alzheimer's disease (AD). (biomedcentral.com)
  • Leucine-rich repeat kinase 2 modulates cyclooxygenase 2 and the inflammatory response in idiopathic and genetic Parkinson's disease. (cdc.gov)
  • Heterogeneity among patients with Parkinson's disease: cluster analysis and genetic association. (cdc.gov)
  • Identification of susceptibility loci for cognitive impairment in a cohort of Han Chinese patients with Parkinson's disease. (cdc.gov)
  • A Specific Diplotype H1j/H2 of the MAPT Gene Could Be Responsible for Parkinson's Disease with Dementia. (cdc.gov)
  • Parkinson's disease is a complex neurodegenerative disorder believed to be caused by a combination of genetic and non-genetic factors. (amp-pd.org)
  • We focus on Alzheimer's disease and Parkinson's disease, two incurable neurodegenerative disorders and experimental paradigms for the age-dependent failure of brain cognitive and motor control in humans. (texaschildrens.org)
  • Expression of human amyloid-beta, Tau, or alpha-synuclein proteins in the fly nervous system recapitulates many core features of Alzheimer's disease and Parkinson's disease pathogenesis. (texaschildrens.org)
  • AD and Parkinson's disease, ALS, schizophrenia) and complex statistical analyses (e.g. gene-wide/burden, pathway analyses). (cardiff.ac.uk)
  • This review will summarize the updated research progress on APOE functions and its role in Alzheimer's disease, Parkinson's disease, cardiovascular diseases, multiple sclerosis, type 2 diabetes mellitus, Type III hyperlipoproteinemia, vascular dementia, and ischemic stroke. (dovepress.com)
  • 3 In this review, we discuss the biological functions of human APOE and its role in Alzheimer's disease (AD), Parkinson's disease (PD), cardiovascular diseases (CVD), multiple sclerosis (MS), type 2 diabetes mellitus (T2DM), vascular dementia (VD), and ischemic (occlusive) stroke (IS). (dovepress.com)
  • What Is Wrong with Balance in Parkinson's Disease? (e-jmd.org)
  • Postural instability and resulting falls are major factors determining quality of life, morbidity, and mortality in individuals with Parkinson's disease (PD). (e-jmd.org)
  • Do cervical stabilization exercises change the effects of conventional exercises in patients with Parkinson's disease? (e-jmd.org)
  • Mutations in the glucocerebrosidase gene (GBA), which cause Gaucher disease, are also potent risk factors for Parkinson's disease. (amsterdamumc.org)
  • In our discovery cohort, the majority of Parkinson's disease cases (56%) have at least one putative damaging variant in a lysosomal storage disorder gene, and 21% carry multiple alleles. (amsterdamumc.org)
  • Our results highlight several promising new susceptibility loci and reinforce the importance of lysosomal mechanisms in Parkinson's disease pathogenesis. (amsterdamumc.org)
  • We suggest that multiple genetic hits may act in combination to degrade lysosomal function, enhancing Parkinson's disease susceptibility. (amsterdamumc.org)
  • Although MSA has been defined as a non-genetic disorder until recently, several multiplex MSA families have been reported, indicating that strong genetic factors confer susceptibility to the disease in multiplex families. (jnss.org)
  • Alzheimer disease (AD) is a neurodegenerative disorder marked by cognitive and behavioral impairment that significantly interferes with social and occupational functioning. (medscape.com)
  • It was reported that K630A mutation in androgen receptor has been shown to cause a loss of acetylation site and has been implicated in Kennedy's disease, an inherited neurodegenerative disorder [8]. (deepdyve.com)
  • Alzheimer's disease (AD) is a progressive neurodegenerative disorder that occurs predominantly in later life. (bmj.com)
  • Alzheimer's disease (AD) is the most common cause of dementia in the elderly, whereas frontotemporal lobar degeneration (FTLD) is the most frequent neurodegenerative disorder with a pre-senile onset. (touchneurology.com)
  • A generalized disorder of nervous system, skeletal muscle and heart resembling Refsum's disease and Hurler's syndrome. (houstonmethodist.org)
  • Alzheimer disease (AD) is an acquired disorder of cognitive and behavioral impairment that markedly interferes with social and occupational functioning. (medscape.com)
  • Linkage analyses of 6 multiplex MSA families revealed several loci showing positive heterogeneity lod (HLOD) scores. (jnss.org)
  • As detailed on our website, the G&E Program tackles foundational questions in development and disease that can be grouped into five research areas: epigenetics, developmental genetics, human genetics, cancer genetics, and genome maintenance and repair. (uth.edu)
  • He moved to UNC in fall of 2004 to continue this work in the Department of Genetics and the Genome Center. (unc.edu)
  • Scholz SW, Bras J. Genetics underlying atypical parkinsonism and related neurodegenerative disorders. (jamanetwork.com)
  • Until recently, our understanding of the genetic causes for human diseases were largely limited to the study of extreme phenotypes produced by Mendelian disorders. (bcm.edu)
  • Alzheimer's disease (AD) is one of the most common neurodegenerative disorders characterized by progressive decline in cognitive function. (biomedcentral.com)
  • Dr. Wilhelmsen's current research activity in this area is devoted to determining how tau mutations produce disease, and the positional cloning of mutations responsible for related disorders. (unc.edu)
  • These studies take advantage of murine models relevant to neurodevelopmental disorders, Parkinson and Huntington diseases, and depression . (igbmc.fr)
  • We find that MGST3 is associated with hippocampus size and is linked to a group of neurodegenerative disorders, such as Alzheimer's. (biomedcentral.com)
  • This wide range of natural variation raises the possibility that susceptibility to a subset of neurodegenerative and psychiatric disorders linked to defects in the hippocampus may depend, in part, on its initial healthy volume. (biomedcentral.com)
  • The most characteristic are frontotemporal degeneration spectrum disorders, but Alzheimer disease and rare disorders such as Creutzfeldt-Jakob disease, CNS Whipple disease, and Niemann-Pick disease type C can be associated with corticobasal syndrome. (medscape.com)
  • Investigation of c9orf72 in 4 neurodegenerative disorders. (cdc.gov)
  • Recent advances have made the discovery of genetic susceptibility loci for complex human phenotypes a reality, including nervous system disorders. (texaschildrens.org)
  • Whole-genome sequencing of an individual with autopsy-proven MSA revealed a homozygous mutation (M78V-V343A) in COQ2. (jnss.org)
  • The Allen Human Brain Atlas (AHBA) provides us comprehensive whole-genome whole-brain microarray transcriptomics data. (biomedcentral.com)
  • The molecular bases of sporadic neurological diseases, however, largely remain unknown. (jnss.org)
  • The availability of next-generation sequencing technologies has made it possible to explore molecular bases of sporadic diseases. (jnss.org)
  • Corticobasal degeneration (CBD), a sporadic neurodegenerative 4-repeat tauopathy, is a pathologically defined entity associated with several clinical phenotypes. (medscape.com)
  • Concerning sporadic AD, it is known that the presence of the ε4 allele of the apolipoprotein E gene is a susceptibility factor. (touchneurology.com)
  • The interactions of multiple single nucleotide polymorphisms (SNPs) are highly hypothesized to affect an individual's susceptibility to complex diseases. (biomedcentral.com)
  • The Wilhelmsen group has been using linkage analysis to map susceptibility loci and determine the phenotype that segregates with the alternative alleles for these loci. (unc.edu)
  • Patients affected by the normal-pressure form of glaucoma are more likely to harbor risk alleles for glaucoma-related optic nerve disease. (prolekarniky.cz)
  • This review focuses on the current knowledge of the pathogenesis of the inflammatory and neurodegenerative elements of the multiple sclerosis plaque. (researchgate.net)
  • Aberrant expression of many specific lncRNAs was reported to be correlated to the pathogenesis of various diseases in human and model animals [ 16 , 17 ]. (researchsquare.com)
  • Evidence for CD4 + T-cell involvement in autoimmune disease pathogenesis and for paracrine calcitriol signaling to CD4 + T lymphocytes is summarized to support the thesis that calcitriol is sunlight's main protective signal transducer in autoimmune disease risk. (frontiersin.org)
  • Research in G&E labs is broadly focused on the fundamental genetic, epigenetic, and genomic mechanisms that control cell growth and differentiation, and that cause cancer and other human diseases. (uth.edu)
  • PRS relies on the cumulative risk from many genomic loci and can be calculated for any number of individuals and get meaningful results. (amp-pd.org)
  • Because both loci influence transforming growth factor beta (TGF-beta) signaling, we performed a genomic pathway analysis that showed an association between the TGF-beta pathway and NPG (permuted p = 0.009). (prolekarniky.cz)
  • GRSs were constructed on the basis of 25 single-nucleotide polymorphisms previously associated with Alzheimer's disease (AD). (biomedcentral.com)
  • A logical extension of this work is to develop the ability to perform genome-wide association analysis, which is being used to identify common sequence variations that affect susceptibility to neurodegeneration. (unc.edu)
  • Our strategy has recently identified cell adhesion converging on the cytoskeleton as likely important for Tau-mediated neurodegeneration and Alzheimer's disease susceptibility, and we are now following up these insights to elucidate the detailed mechanisms. (texaschildrens.org)
  • Alcohol and Alzheimer's Disease-Does Alcohol Dependence Contribute to Beta-Amyloid Deposition, Neuroinflammation and Neurodegeneration in Alzheimer's Disease? (wineinformationcouncil.eu)
  • We have performed a meta-analysis of two independent genome-wide association studies for primary open angle glaucoma (POAG) followed by a normal-pressure glaucoma (NPG, defined by intraocular pressure (IOP) less than 22 mmHg) subgroup analysis. (prolekarniky.cz)
  • The disease was originally described by Alois Alzheimer and Gaetano Perusini in 1906, and it is clinically characterised by progressive cognitive impairment including impaired judgement, decision-making and orientation, often accompanied, in later stages, by psychobehavioural disturbances as well as language impairment. (touchneurology.com)
  • We evaluated a risk index comprising lifestyle, medical and demographic factors (the Australian National University Alzheimer's Disease Risk Index [ANU-ADRI]), as well as a genetic risk score (GRS), for assessment of the risk of progression to mild cognitive impairment (MCI). (biomedcentral.com)
  • Accurate risk assessment for cognitive impairment and dementia is increasingly important, given the current lack of effective disease-modifying treatments for Alzheimer's disease (AD) and other dementias. (biomedcentral.com)
  • AIMS: To investigate the underlying neurobiology between alcohol use, misuse and dependence and cognitive impairment, particularly Alzheimer's disease (AD). (wineinformationcouncil.eu)
  • To demonstrate the promise of our approach, we apply it to the integrative analysis of the brain transcriptome data from the Allen Human Brain Atlas (AHBA) and the amyloid imaging data from the Alzheimer's Disease Neuroimaging Initiative (ADNI) cohort. (biomedcentral.com)
  • Multiple system atrophy (MSA) is a progressive neurodegenerative disease with 12,000 patients in Japan, which is clinically characterized by autonomic failure in addition to various combinations of parkinsonism, and cerebellar ataxia. (jnss.org)
  • Although his group has mapped the loci for many traits, Dr. Wilhelmsen's original identification of linkage of the syndrome disinhibition-dementia-parkinsonism-amyotrophy complex (DDPAC) to 17q21-22 (now called FTDP-17) had a key role in setting the direction for his future research. (unc.edu)
  • His attraction to the DDPAC phenotype was the wide clinical spectrum of disease presentation (including dementia, motor neuron disease, parkinsonism, alcoholism and behaviors similar to schizophrenia) seen in individuals with the same mutation. (unc.edu)
  • Linkage analysis for four large-scale family based projects has been completed and loci have been identified for a series of addiction and personality related phenotypes. (unc.edu)
  • The goal is to understand how discrete developmental events contribute to physiological diversity in cognitive performance, or affective susceptibility to stress, and understand the neurodevelopmental basis of neurologic diseases. (igbmc.fr)
  • Our research integrates genetic investigation in human subjects and model organisms, with the goal of understanding brain function and aging, and improving the treatment of neurologic disease. (texaschildrens.org)
  • We annotated targets and eligibility criteria for 3238 neurodegenerative disease trials registered at ClinicalTrials.gov from 2000 to 2020. (nature.com)
  • We used a previously validated multiplexed 10-min, targeted proteomic assay to assess 54 candidate cerebrospinal fluid (CSF) biomarkers in two independent cohorts comprising individuals with neurodegenerative dementias and healthy controls. (lu.se)
  • A deep understanding of molecular mechanisms relevant to gene-environment interactions is needed to deliver etiology-based autoimmune disease prevention and treatment strategies. (frontiersin.org)
  • A deep understanding of disease mechanisms will be needed to deliver etiology-based strategies to reverse this vexing trend. (frontiersin.org)
  • Gene-environment interactions, sunlight and vitamin D, and T lymphocytes as autoimmune disease initiators and vitamin D targets are discussed to explain the rationale for reviewing vitamin D mechanisms in T cells. (frontiersin.org)
  • Finally, unanswered questions relating to vitamin D mechanisms in CD4 + T cells are highlighted to promote further research that may lead to a deeper understanding of autoimmune disease molecular etiology. (frontiersin.org)
  • We drew mainly on MS and T1D research because intensive investigation has generated detailed insights into vitamin D mechanisms in these diseases and provided valuable guidance for research on other autoimmune diseases. (frontiersin.org)
  • A recent chapter ( 6 ) and a review ( 7 ) have summarized vitamin D mechanisms in autoimmune diseases more generally. (frontiersin.org)
  • CONCLUSION: We propose alcohol adds to the cognitive burden seen in dementia through additional mechanisms to neurodegenerative processes or may contribute at various mechanistic points in the genesis and sustenance of AD pathology via neuroinflammation. (wineinformationcouncil.eu)
  • We find that PM20D1 is a methylation and expression quantitative trait locus coupled to an AD-risk associated haplotype, which displays enhancer-like characteristics and contacts the PM20D1 promoter via a haplotype-dependent, CCCTC-binding-factor-mediated chromatin loop. (nature.com)
  • To our knowledge, this is the first genetic locus associated with both cancer risk and WHR. (ox.ac.uk)
  • Goran MI, Ball GDC, Cruz ML. Obesity and risk of type 2 diabetes and cardiovascular disease in children and adolescents. (medigraphic.com)
  • Exploring known genetic loci can shed light on this complicated issue and provide new ways to explore genetic risk for an individual or group of individuals. (amp-pd.org)
  • It is expected that a true biomarker of risk or disease will more likely be present in persons with a high PRS than with a low PRS. (amp-pd.org)
  • Evidence linking sunlight, vitamin D, and the risk of multiple sclerosis and type 1 diabetes is summarized to develop the thesis that vitamin D is the environmental factor that most strongly influences autoimmune disease development. (frontiersin.org)
  • Multiple sclerosis and T1D have distinct target organs, genetic risk factors, onset ages, and female to male ratios, but target organ-specific T cells as initiators unite these diseases. (frontiersin.org)
  • Although possession of the ε4 allele of the apolipoprotein E gene appears to be an important biological marker for Alzheimer's disease (AD) susceptibility, strong evidence indicates that at least one additional risk gene exists on chromosome 12. (bmj.com)
  • Since then, the consortium she leads, GERAD (Genetic and Environmental Risk in Alzheimer's Disease), has continued the momentum and has played a leading role in further discoveries. (cardiff.ac.uk)
  • Targeting APOE may be a potential approach for diagnosis, risk assessment, prevention, and treatment of various neurodegenerative and cardiovascular diseases in humans. (dovepress.com)
  • Employing successful intervention and treatment strategies focused on disease prevention is currently the only available approach that can have an impact on the projected rates of dementia, with risk assessment being a key component of population-based risk reduction for identification of at-risk individuals. (biomedcentral.com)
  • Joint mouse-human phenome-wide association to test gene function and disease risk. (genenetwork.org)
  • It has been proposed that early age at menopause is a risk factor for osteoporosis and cardiovascular disease, whereas later age at menopause is a risk fac. (biomedcentral.com)
  • During the past three decades, we have witnessed remarkable advances in understanding the molecular bases of hereditary neurological diseases by "positional cloning" strategies. (jnss.org)
  • A complementary approach directly leverages the underlying disease pathology as an intermediate trait, or endophenotype. (bcm.edu)
  • Although two percent of the population over age 65 are clinically diagnosed with PD, the defining pathology of disease (alpha-synuclein Lewy bodies) is discovered in 20 percent of brains from population-based autopsy studies. (bcm.edu)
  • Our empirical study on the AHBA and ADNI data shows the promise of the approach, and the resulting AD gene discoveries provide valuable information for better understanding biological pathways from transcriptomic signatures to intermediate brain traits and to phenotypic disease outcomes. (biomedcentral.com)
  • Importantly, TNF-blocking drugs can promote onset or exacerbation of MS, but they have proven highly efficacious in the treatment of autoimmune diseases for which there is no association with rs1800693. (researchgate.net)
  • The global burden has risen with the near tripling in the last half-century of multiple sclerosis (MS) ( 2 , 3 ), type 1 diabetes (T1D) ( 4 ), and other autoimmune diseases. (frontiersin.org)
  • This review highlights recent advances in vitamin D and T-lymphocyte biology in an effort to harness vitamin D's potential to reduce the impact of autoimmune diseases. (frontiersin.org)
  • Autoimmune diseases represent a failure of self-identification leading to an immune-mediated assault on host tissues. (frontiersin.org)
  • Other autoimmune diseases are included where robust mechanistic data exist. (frontiersin.org)
  • We have ongoing interests in the systems level analysis and reconstruction of regulatory networks, inference of enhancer-promoter contacts, predictive models of gene expression and integration of three-dimensional chromatin structure with one-dimensional epigenetic measurements in the context of cancer, malaria, asthma and several autoimmune diseases. (ucsd.edu)
  • Second, while reports sometimes categorize trials as preventive versus symptomatic, we wished to examine more quantitative metrics of disease stage or severity. (nature.com)
  • Understanding the genetic factors that contribute to individual differences in hippocampal volume is thus crucial in providing insight into vulnerability and severity of disease. (biomedcentral.com)
  • A number of additional genetic factors contribute to susceptibility for AD and FTLD. (touchneurology.com)
  • Coronal T1-weighted magnetic resonance imaging (MRI) scan in a patient with moderate Alzheimer disease. (medscape.com)
  • This resembles the β-amyloid precursor protein (APP) in Alzheimer disease (AD), which can be physiologically processed by α-, β-, and γ-secretases. (mdpi.com)
  • Although Alzheimer disease (AD) is more frequent in individuals with Down syndrome (DS), the main contributing factor is unknown. (medscape.com)
  • and further, our genome scan implicates common variation in the amyloid precursor protein (APP) gene (Shulman et al. (bcm.edu)
  • Only two common susceptibility loci for RCC have been confirmed to date. (ox.ac.uk)
  • Multiple sclerosis (MS) is a common autoimmune disease that targets myelin in the central nervous system (CNS). (researchgate.net)
  • Primary open angle glaucoma (POAG), the most common form of glaucoma in the Western world, is an age-related, complex disease characterized by progressive irreversible degeneration of the optic nerve due to apoptotic retinal ganglion cell death [2] . (prolekarniky.cz)
  • We also participate in collaborative studies for the functional genetic dissection of Alzheimer's disease, focusing on the responsible neuropathology, amyloid neuritic plaques and Tau neurofibrillary tangles. (texaschildrens.org)
  • Indeed, "functional and mechanistic work on the molecular etiology of disease remains one of the major challenges in modern biology" ( 5 ). (frontiersin.org)
  • We develop methods that are based in statistics, machine learning, optimization and graph theory to understand how changes in the 3D genome affect cellular outcome such as development, differentiation and gene expression. (ucsd.edu)
  • Understanding the mutations in APOE, their structural properties, and their isoforms is important to determine its role in various diseases and to advance the development of therapeutic strategies. (dovepress.com)
  • Neurodegenerative disease is on the rise globally due to aging populations 1 , highlighting a need for effective therapeutic interventions. (nature.com)
  • It is an incurable disease with a long preclinical period and progressive course. (medscape.com)