Search results for " Variant"

showing 10 items of 231 documents

Comparison of HapMap and 1000 genomes reference panels in a large-scale genome-wide association study

2017

An increasing number of genome-wide association (GWA) studies are now using the higher resolution 1000 Genomes Project reference panel (1000G) for imputation, with the expectation that 1000G imputation will lead to the discovery of additional associated loci when compared to HapMap imputation. In order to assess the improvement of 1000G over HapMap imputation in identifying associated loci, we compared the results of GWA studies of circulating fibrinogen based on the two reference panels. Using both HapMap and 1000G imputation we performed a meta-analysis of 22 studies comprising the same 91,953 individuals. We identified six additional signals using 1000G imputation, while 29 loci were ass…

Netherlands Twin Register (NTR)0301 basic medicineGlycobiologySocial Scienceslcsh:MedicineGenome-wide association study030105 genetics & heredityBiochemistryMathematical and Statistical TechniquesSociologyCell SignalingConsortiaGENETIC-VARIANTSMedicine and Health SciencesIMPUTATIONInternational HapMap Projectlcsh:ScienceGeneticsMultidisciplinaryCOMMON VARIANTSGenomicsMultidisciplinary SciencesINSIGHTSCARDIOVASCULAR-DISEASEPhysical SciencessymbolsScience & Technology - Other TopicsHealth Services ResearchGenomic Signal ProcessingStatistics (Mathematics)Research ArticleSignal TransductionGenotypingSUSCEPTIBILITY LOCIGeneral Science & TechnologyBIOLOGYSingle-nucleotide polymorphismGenomicsHapMap ProjectComputational biologyPRESSUREBiologyResearch and Analysis Methods03 medical and health sciencessymbols.namesakeMD MultidisciplinaryGenome-Wide Association StudiesGeneticsJournal Article/dk/atira/pure/keywords/cohort_studies/netherlands_twin_register_ntr_HumansStatistical Methods1000 Genomes ProjectMolecular Biology TechniquesMolecular BiologyMETAANALYSISGlycoproteinsScience & Technologylcsh:RHuman GenomeCONSORTIUMBiology and Life SciencesComputational BiologyFibrinogenHuman GeneticsCell BiologyComparative GenomicsGenome AnalysisHealth Care030104 developmental biologyBonferroni correctionlcsh:QHaplotype estimationMathematicsImputation (genetics)Meta-AnalysisGenome-Wide Association Study
researchProduct

Defining the role of common variation in the genomic and biological architecture of adult human height

2014

Item does not contain fulltext Using genome-wide data from 253,288 individuals, we identified 697 variants at genome-wide significance that together explained one-fifth of the heritability for adult height. By testing different numbers of variants in independent studies, we show that the most strongly associated approximately 2,000, approximately 3,700 and approximately 9,500 SNPs explained approximately 21%, approximately 24% and approximately 29% of phenotypic variance. Furthermore, all common variants together captured 60% of heritability. The 697 variants clustered in 423 loci were enriched for genes, pathways and tissue types known to be involved in growth and together implicated genes…

Netherlands Twin Register (NTR)BIO/12 - BIOCHIMICA CLINICA E BIOLOGIA MOLECOLARE CLINICAElectronic Medical Records and Genomics (eMEMERGEGE) ConsortiumMedizinGenome-wide association studyAdult; Analysis of Variance; Body Height/genetics; European Continental Ancestry Group/genetics; Genetic Variation/genetics; Genetics Population; Genome-Wide Association Study/methods; Humans; Oligonucleotide Array Sequence Analysis; Polymorphism Single Nucleotide/geneticsheritability0302 clinical medicineGenome-wideEuropean Continental Ancestry Group/geneticsSNPSOligonucleotide Array Sequence AnalysissnpsGenetics & Heredityddc:616GeneticsMedical And Health Sciences0303 health scienceseducation.field_of_studyvariantsBody Height/geneticsGENETIC-VARIATIONBiological SciencesPolymorphism Single Nucleotide/geneticsGenetic Variation/geneticsUrological cancers Radboud Institute for Health Sciences [Radboudumc 15]Genome-Wide Association Study/methodsbody heightgenetic-variationLife Sciences & BiomedicineSingle Nucleotide/geneticsHumanAdultEuropean Continental Ancestry GroupPopulationPopulationSingle-nucleotide polymorphismBiologyPolymorphism Single NucleotideArticleWhite PeopleNOcomplex traits03 medical and health sciencesGenetic variationheritability adult height/dk/atira/pure/keywords/cohort_studies/netherlands_twin_register_ntr_GeneticsHumansPolymorphismHuman heightPAGEGE ConsortiumeducationGeneVLAG030304 developmental biologyGlobal NutritionWereldvoedingAnalysis of VarianceGenome-wide; heritability; variantsgenome-wide association studyScience & TechnologyWhitesOligonucleotide Array Sequence AnalysiMUTATIONSCOMPLEX TRAITSta1184Klinisk medicinpopulation geneticsGenetic VariationHeritabilityta3121mutationsGenetic architectureBody HeightGenetics Populationgenetic variationMIGen ConsortiumInflammatory diseases Radboud Institute for Health Sciences [Radboudumc 5]Clinical Medicine030217 neurology & neurosurgeryheightLifeLines Cohort StudyDevelopmental BiologyGenome-Wide Association StudyNature genetics
researchProduct

Meta-Analysis of Genome-Wide Association Studies in >80 000 Subjects Identifies Multiple Loci for C-Reactive Protein Levels

2011

Background— C-reactive protein (CRP) is a heritable marker of chronic inflammation that is strongly associated with cardiovascular disease. We sought to identify genetic variants that are associated with CRP levels. Methods and Results— We performed a genome-wide association analysis of CRP in 66 185 participants from 15 population-based studies. We sought replication for the genome-wide significant and suggestive loci in a replication panel comprising 16 540 individuals from 10 independent studies. We found 18 genome-wide significant loci, and we provided evidence of replication for 8 of them. Our results confirm 7 previously known loci and introduce 11 novel loci that are implicated in p…

Netherlands Twin Register (NTR)Genome-wide association studyDisease030204 cardiovascular system & hematology0302 clinical medicineDESIGNRisk FactorsFRAMINGHAMNETHERLANDS TWIN REGISTERgeneticsCRP GENE2. Zero hungerGenetics0303 health scienceseducation.field_of_studybiologyCOMMON VARIANTS3. Good healthHNF1AC-Reactive Proteinmyocardial infarctionCardiovascular DiseasesMeta-analysis/dk/atira/pure/sustainabledevelopmentgoals/good_health_and_well_beingCardiology and Cardiovascular MedicineVasculitisPopulationArticle03 medical and health sciencesINFLAMMATIONSDG 3 - Good Health and Well-beingPhysiology (medical)/dk/atira/pure/keywords/cohort_studies/netherlands_twin_register_ntr_medicineHumansGenetic Predisposition to DiseaseCORONARY-HEART-DISEASEALPHA-GENEeducation030304 developmental biologyGenetic associationEPIDEMIOLOGIC APPLICATIONSgenome-wide association studyC-reactive proteinmedicine.diseasemeta-analysisinflammationbiology.proteinGENETICALLY ISOLATED POPULATIONMetabolic syndromeBiomarkers
researchProduct

Cultural institutions as agents of urban and community regeneration in the (post-)pandemic city. The case of the «Laboratorio Zen Insieme» in Palermo

2022

Although all cities in the world have been affected by the COVID-19 pandemic, its impacts on the territories, yet to be understood, are unevenly distributed, revealing extremely varied imbalances depending on the places. However, it is clear that the virus and its variants have aggravated pre-existing socio-spatial inequalities, creating new ones and bringing attention back to those implications between space, planning, public health and citizenship that are at the origins of contemporary urbanism. In a reference framework in which the crisis is globalized but unequal and in the absence of a welfare system capable of responding to the urgencies of the most marginalized social contexts and g…

Olsen 2018Settore ICAR/21 - UrbanisticaSettore M-GGR/01 - GeografiaSacco and Blessi 2009). In the current (post-) pandemic context and through the lens of a southern European perspective the purpose of this article is to critically reflect about the role of culture as possible vehicle of urban and community regeneration. In particular we will focus on the activities of the no profit organization «Laboratorio Zen Insieme» in ZEN2 one of the last large popular and peripheral neighborhoods built in Palermo at the end of 80s in order to explore and understand how cultural practices work as agent of urban and social transformation capable of addressing emerging issues especially in the pandemic scenario we are experiencing. Thecasestudy has been conducted through analysis of documents participative observations (Honer and Hitzler 2015) and qualitative in-depth interviews with key actors involved in the conception organization and management of the activities carried out by Laboratorio Zen Insieme with representatives of local institutions and non-formal conversations with participants of the workshops heldin the neighborhood. The experience we narrate finds that cultural practices have re-conceptualized their design and functions as strategies of urban and community regeneration and at the same time have contributed to answer to emergent issues in developing proximity and local based strategies facing up to problems inherent civil rights educationalpoverty socio-spatial justice and have changed the image and identity of urban places they inhabit.In this sense the research provides a framework for development of strategies and legitimization for cultural practices and a point of discussionabouttheirrolein urban development.Although all cities in the world have been affected by the COVID-19 pandemic its impacts on the territories yet to be understood are unevenly distributed revealing extremely varied imbalances depending on the places. However it is clear that the virus and its variants have aggravated pre-existing socio-spatial inequalities creating new ones and bringing attention back to those implications between space planning public health and citizenship that are at the origins of contemporary urbanism. In a reference framework in which the crisis is globalized but unequal and in the absence of a welfare system capable of responding to the urgencies of the most marginalized social contexts and groups a response to the new social and individual needs has been offered by cultural institutions that play a role of territorial agency often independently or in the absence of political institutions. Far from the idea of entertainment and divertissement it is in fact increasingly clear how the practices of cultural innovation experimenting with various forms of action and participation can in some cases play a fundamental role in the processes of social cohesion and community building representing an antidote to the worsening of the phenomena of marginalization and socio-spatial inequalities within cities and territories (Colantonio and Dixon 2011
researchProduct

The rapid spread of SARS-COV-2 Omicron variant in Italy reflected early through wastewater surveillance

2022

The SARS-CoV-2 Omicron variant emerged in South Africa in November 2021, and has later been identified worldwide, raising serious concerns. A real-time RT-PCR assay was designed for the rapid screening of the Omicron variant, targeting characteristic mutations of the spike gene. The assay was used to test 737 sewage samples collected throughout Italy (19/21 Regions) between 11 November and 25 December 2021, with the aim of assessing the spread of the Omicron variant in the country. Positive samples were also tested with a real-time RT-PCR developed by the European Commission, Joint Research Centre (JRC), and through nested RT-PCR followed by Sanger sequencing. Overall, 115 samples tested po…

Omicron; RT-qPCR; SARS-CoV-2; Sewage; Variant; Wastewater-based epidemiologyWastewater-Based Epidemiological MonitoringEnvironmental EngineeringSewageSARS-CoV-2OmicronRT-qPCRCOVID-19Wastewater-based epidemiologyWastewaterPollutionOmicron; RT-qPCR; SARS-CoV-2; Sewage; Variant; Wastewater-based epidemiology; Humans; RNA Viral; Sewage; Waste Water; Wastewater-Based Epidemiological Monitoring; COVID-19; SARS-CoV-2SARS-Cov2RNA ViralEnvironmental ChemistryRNAHumansWaste WaterViralwastewater based epidemiologyVariantWaste Management and DisposalHumanOmicron RT-qPCR SARS-CoV-2 Sewage Variant Wastewater-based epidemiology
researchProduct

The Detection of Androgen Receptor Splice Variant 7 in Plasma-derived Exosomal RNA Strongly Predicts Resistance to Hormonal Therapy in Metastatic Pro…

2017

Abstract Background The androgen receptor splice variant 7 (AR-V7) is associated with resistance to hormonal therapy in castration-resistant prostate cancer (CRPC). Due to limitations of the methods available for AR-V7 analysis, the identification of a reliable detection method may facilitate the use of this biomarker in clinical practice. Objective To confirm AR-V7 as a predictor of resistance to hormonal therapy and develop a new approach to assess AR-V7 by highly sensitive digital droplet polymerase chain reaction (ddPCR) in plasma-derived exosomal RNA. Design, setting, and participants Plasma samples were collected from 36 CRPC patients before they began second-line hormonal treatment. …

Oncology0301 basic medicineMaleResistanceExosomeschemistry.chemical_compoundProstate cancer0302 clinical medicineProtein IsoformsNeoplasm MetastasisReceptorAged 80 and overProstate cancerMiddle AgedProstatic Neoplasms Castration-ResistantReceptors Androgen030220 oncology & carcinogenesisBenzamidesAdenocarcinomaBiomarker (medicine)Hormonal therapyAR-V7; Digital droplet PCR; Exosomes; Hormonal therapy; Pharmacogenetics; Prostate cancer; Resistance; UrologyAndrostenesHormonal therapymedicine.medical_specialtyAntineoplastic Agents Hormonalmedicine.drug_classUrologyCastration resistantAdenocarcinomaDisease-Free Survival03 medical and health sciencesSDG 3 - Good Health and Well-beingInternal medicineNitrilesPhenylthiohydantoinmedicineEnzalutamideHumansAgedDigital droplet PCRPlasma derivedbusiness.industryRNAAndrogen Receptor Splice Variant 7medicine.diseaseAndrogenEndocrinology030104 developmental biologychemistryPharmacogeneticsDrug Resistance NeoplasmCancer cellCancer researchRNAAR-V7businessPharmacogenetics
researchProduct

Special Situations in APL

2017

The introduction of all-trans-retinoic acid (ATRA) and arsenic trioxide (ATO) as the mainstay therapy of acute promyelocytic leukemia (APL) has drastically changed the outcome of this hematologic malignancy into one of the first to receive a targeted treatment. Using frontline treatment strategies including these agents in combination with standard cytotoxic drugs has provided outstanding therapeutic results in most patients. In spite of the achievement of brilliant results in the majority of patients, some special situations still require the implementation of changes from the conventional therapeutic approach. In this chapter, we will review and discuss the management of APL in older and …

OncologyAcute promyelocytic leukemiamedicine.medical_specialtybusiness.industryGenetic variantsmedicine.diseaseLeukemiachemistry.chemical_compoundTherapeutic approachchemistryOlder patientsInternal medicinemedicineHematologic malignancyTreatment strategyArsenic trioxidebusiness
researchProduct

Identification of a genetic signature enriching for response to ibrutinib in relapsed/refractory follicular lymphoma in the DAWN phase 2 trial.

2021

Abstract Background The single‐arm DAWN trial (NCT01779791) of ibrutinib monotherapy in patients with relapsed/refractory follicular lymphoma (FL) showed an overall response rate (ORR) of 20.9% and a median response duration of 19.4 months. This biomarker analysis of the DAWN dataset sought to determine genetic classifiers for prediction of response to ibrutinib treatment. Methods Whole exome sequencing was performed on baseline tumor samples. Potential germline variants were excluded; a custom set of 1216 cancer‐related genes was examined. Responder‐ versus nonresponder‐associated variants were identified using Fisher's exact test. Classifiers with increasing numbers of genes were created …

OncologyCancer ResearchFollicular lymphomaBiochemistrychemistry.chemical_compoundGenetic signaturePiperidinesRecurrenceMedicineExomeLymphoma FollicularExome sequencingRC254-282Research ArticlesNeoplasms. Tumors. Oncology. Including cancer and carcinogensHematologyDNA-Binding ProteinsExact testOncologyIbrutinibRefractory Follicular LymphomaClin oncolResearch ArticleGenetic Markersmedicine.medical_specialtyImmunologyAntineoplastic AgentslymphomaBiologyGermline mutationInternal medicinePartial responseExome SequencingHumansRadiology Nuclear Medicine and imagingIn patientbusiness.industryAdeninegenetic variantsClinical Cancer ResearchbiomarkersCell Biologymedicine.diseasemutationsFANCAMutational analysisCARD Signaling Adaptor ProteinschemistryGuanylate CyclaseFamily medicineRelapsed refractoryMutationbusinessCancer medicine
researchProduct

Common Breast Cancer Susceptibility Alleles and the Risk of Breast Cancer for BRCA1 and BRCA2 Mutation Carriers: Implications for Risk Prediction

2010

Abstract The known breast cancer susceptibility polymorphisms in FGFR2, TNRC9/TOX3, MAP3K1, LSP1, and 2q35 confer increased risks of breast cancer for BRCA1 or BRCA2 mutation carriers. We evaluated the associations of 3 additional single nucleotide polymorphisms (SNPs), rs4973768 in SLC4A7/NEK10, rs6504950 in STXBP4/COX11, and rs10941679 at 5p12, and reanalyzed the previous associations using additional carriers in a sample of 12,525 BRCA1 and 7,409 BRCA2 carriers. Additionally, we investigated potential interactions between SNPs and assessed the implications for risk prediction. The minor alleles of rs4973768 and rs10941679 were associated with increased breast cancer risk for BRCA2 carrie…

OncologyCancer Researchendocrine system diseasesVesicular Transport ProteinsGene mutation0302 clinical medicineRisk FactorsGenotypeskin and connective tissue diseasesAged 80 and over0303 health sciencesBRCA1 ProteinHigh Mobility Group ProteinsMiddle Aged3. Good healthOncology030220 oncology & carcinogenesisFemaleBreast diseaseReceptors ProgesteroneAdultHeterozygotemedicine.medical_specialtyGenotypeBreast NeoplasmsSingle-nucleotide polymorphismBiologyPolymorphism Single NucleotideRisk AssessmentArticle03 medical and health sciencesBreast cancerSDG 3 - Good Health and Well-beingInternal medicinemedicineHumansGenetic Predisposition to DiseaseAllelesAged030304 developmental biologyBRCA2 ProteinHereditary cancer and cancer-related syndromes [ONCOL 1]Sodium-Bicarbonate SymportersHaplotypeCancergenome-wide association estrogen-receptor loci variantsmedicine.diseaseSurvival AnalysisTOX3MutationTrans-ActivatorsCancer researchApoptosis Regulatory Proteins
researchProduct

Impact of deleterious variants in other genes beyond BRCA1/2 detected in breast/ovarian and pancreatic cancer patients by NGS-based multi-gene panel …

2021

Background Hereditary breast cancer (BC), ovarian cancer (OC), and pancreatic cancer (PC) are the major BRCA-associated tumours. However, some BRCA1/2-wild-type (wt) patients with a strong personal and/or family history of cancer need a further genetic testing through a multi-gene panel containing other high- and moderate-risk susceptibility genes. Patients and methods Our study was aimed to assess if some BC, OC, or PC patients should be offered multi-gene panel testing, based on well-defined criteria concerning their personal and/or family history of cancer, such as earliness of cancer onset, occurrence of multiple tumours, or presence of at least two or more affected first-degree relativ…

OncologyCancer Researchmedicine.medical_specialtySettore MED/06 - Oncologia MedicaPALB2pancreatic cancerBreast NeoplasmsBreast cancerbreast cancerMUTYHInternal medicinePancreatic cancerMedicineHumansGenetic Predisposition to DiseaseGenetic TestingFamily historyCHEK2Original ResearchGenetic testingOvarian Neoplasmsmedicine.diagnostic_testbusiness.industryBRCA1 ProteinCancermedicine.diseasePancreatic Neoplasmsovarian cancerOncologymulti-gene panel testingFemalegermline pathogenic variantsbusiness
researchProduct