0000000000414494

AUTHOR

Norman Klopp

showing 8 related works from this author

Meta-analysis of genome-wide association studies from the CHARGE consortium identifies common variants associated with carotid intima media thickness…

2011

Carotid intima media thickness (cIMT) and plaque determined by ultrasonography are established measures of subclinical atherosclerosis that each predicts future cardiovascular disease events. We conducted a meta-analysis of genome-wide association data in 31,211 participants of European ancestry from nine large studies in the setting of the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Consortium. We then sought additional evidence to support our findings among 11,273 individuals using data from seven additional studies. In the combined meta-analysis, we identified three genomic regions associated with common carotid intima media thickness and two different regions a…

AgingMultifunction cardiogramGenome-wide association studyDiseaseCoronary Artery Disease030204 cardiovascular system & hematologyCarotid Intima-Media ThicknessCoronary artery diseaseCohort Studies0302 clinical medicinecardiovascular diseaseRisk FactorsAging/geneticsgeneticsMyocardial infarctionEuropean Continental Ancestry Group/geneticsriskPlaque0303 health scienceseducation.field_of_studyGenomeCoronary Artery Disease/geneticsHeartSingle NucleotidePlaque Atherosclerotic/geneticsMiddle AgedPlaque Atherosclerotic3. Good healthPhenotypeHeart/physiopathologyCardiologyHumanAdultmedicine.medical_specialtygenetic epidemiologyGenotypesubclinical atherosclerosisPopulationSingle-nucleotide polymorphismBiologyPolymorphism Single NucleotideWhite PeopleArticle03 medical and health sciencesSDG 3 - Good Health and Well-beingInternal medicinemedicinecohort studyHumanscarotid intima media thicknessGenetic Predisposition to DiseasePolymorphismeducation030304 developmental biologyAgedAtherosclerotic/geneticsGenome Humanmedicine.diseaseAtherosclerosismeta-analysisAtherosclerosis/geneticsIntima-media thicknessGenetic LociGenome-Wide Association Study
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Duffy antigen receptor for chemokines (Darc) polymorphism regulates circulating concentrations of monocyte chemoattractant protein-1 and other inflam…

2010

AbstractTo identify the genetic basis of circulating concentrations of monocyte chemoattractant protein-1 (MCP-1), we conducted genome-wide association analyses for MCP-1 in 3 independent cohorts (n = 9598). The strongest association was for serum MCP-1 with a nonsynonymous polymorphism, rs12075 (Asp42Gly) in DARC, the gene for Duffy antigen receptor for chemokines, a known vascular reservoir of proinflammatory cytokines (minor allele frequency, 45.6%; P < 1.0 * 10−323). This association was supported by family-based genetic linkage at a locus encompassing the DARC gene (genome-wide P = 8.0 * 10−13). Asp42Gly accounted for approximately 20% of the variability in serum MCP-1 concentration…

AdultMaleCCR2ChemokineErythrocytesImmunologyReceptors Cell SurfacePolymorphism Single NucleotideBiochemistryProinflammatory cytokineCohort StudiesmedicineHumansCytokine bindingReceptorInterleukin 6Chemokine CCL2biologyMonocyteCell BiologyHematologyMiddle AgedMolecular biologymedicine.anatomical_structureChromosomes Human Pair 1Genetic LociImmunologybiology.proteinFemaleInterleukin 18Inflammation MediatorsDuffy Blood-Group SystemGenome-Wide Association StudyBlood
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Genome-wide association analyses identify 18 new loci associated with serum urate concentrations

2013

Elevated serum urate concentrations can cause gout, a prevalent and painful inflammatory arthritis. By combining data from >140,000 individuals of European ancestry within the Global Urate Genetics Consortium (GUGC), we identified and replicated 28 genome-wide significant loci in association with serum urate concentrations (18 new regions in or near TRIM46, INHBB, SFMBT1, TMEM171, VEGFA, BAZ1B, PRKAG2, STC1, HNF4G, A1CF, ATXN2, UBE2Q2, IGF1R, NFAT5, MAF, HLF, ACVR1B-ACVRL1 and B3GNT4). Associations for many of the loci were of similar magnitude in individuals of non-European ancestry. We further characterized these loci for associations with gout, transcript expression and the fractional…

Candidate geneInhibins/geneticsGenome-wide association studyGENETIC-LOCIchemistry.chemical_compound0302 clinical medicineserum urateGene FrequencyGout/bloodassociation analysis serum urateGlucose/metabolismSettore MED/14 - NEFROLOGIAHyperuricemiaserum; urate; genePOPULATIONMETABOLIC SYNDROMEGenetics0303 health scienceseducation.field_of_studybiologyPolymorphism Single Nucleotide/genetics3. Good healthHYPERURICEMIAGenetic Loci/genetics/dk/atira/pure/sustainabledevelopmentgoals/good_health_and_well_beingSLC22A12Single Nucleotide/geneticsSNPsSignal TransductionMOLECULAR PHYSIOLOGYserum urate concentrations gout genome-wide meta-analysisEuropean Continental Ancestry GroupPopulationPolymorphism Single NucleotideWhite PeopleUric Acid/bloodserum urate concentrationsgenome-wide meta-analysis03 medical and health sciencesSDG 3 - Good Health and Well-beinguric acidGeneticsmedicineHumansInhibinsPolymorphismeducation030304 developmental biology030203 arthritis & rheumatologyAnalysis of VarianceGOUTIDENTIFICATIONTRANSPORTERCARDIOVASCULAR-DISEASE RISKta3121medicine.diseaseassociation analysisGoutmeta-analysisGlucosechemistryGenetic Locigenome-wide association studiesbiology.proteinSignal Transduction/geneticsUric acidURIC-ACID LEVELSGenome-Wide Association StudySLC2A9
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Genetic risk and a primary role for cell-mediated immune mechanisms in multiple sclerosis.

2011

Multiple sclerosis is a common disease of the central nervous system in which the interplay between inflammatory and neurodegenerative processes typically results in intermittent neurological disturbance followed by progressive accumulation of disability. Epidemiological studies have shown that genetic factors are primarily responsible for the substantially increased frequency of the disease seen in the relatives of affected individuals, and systematic attempts to identify linkage in multiplex families have confirmed that variation within the major histocompatibility complex (MHC) exerts the greatest individual effect on risk. Modestly powered genome-wide association studies (GWAS) have ena…

Immunity Cellular/geneticsCellular immunityMultiple SclerosisGenome-wide association studyCLEC16ABiologyPolymorphism Single NucleotideCell Differentiation/immunologyEurope/ethnologyMajor Histocompatibility Complex/geneticsMajor Histocompatibility Complex03 medical and health sciences0302 clinical medicinemedicineGenetic predispositionHumansGenetic Predisposition to DiseaseHLA-A Antigens/geneticsAlleles030304 developmental biologyGenetic associationGenetics0303 health sciencesImmunity CellularMultidisciplinaryHLA-A AntigensGenome HumanMultiple sclerosisGenetic Predisposition to Disease/geneticsHLA-DR Antigens/geneticsLymphocyte differentiationCell DifferentiationHLA-DR AntigensT-Lymphocytes Helper-InducerRC346medicine.diseasePolymorphism Single Nucleotide/geneticsGenetic architecture3. Good healthEuropeSample SizeImmunologyGenome Human/geneticsMultiple Sclerosis/genetics030217 neurology & neurosurgeryT-Lymphocytes Helper-Inducer/cytologyGenome-Wide Association StudyHLA-DRB1 Chains
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Genome-wide association and large-scale follow up identifies 16 new loci influencing lung function

2011

Pulmonary function measures reflect respiratory health and are used in the diagnosis of chronic obstructive pulmonary disease. We tested genome-wide association with forced expiratory volume in 1 second and the ratio of forced expiratory volume in 1 second to forced vital capacity in 48,201 individuals of European ancestry with follow up of the top associations in up to an additional 46,411 individuals. We identified new regions showing association (combined P < 5 x 10(-8)) with pulmonary function in or near MFAP2, TGFB2, HDAC4, RARB, MECOM (also known as EVI1), SPATA9, ARMC2, NCR3, ZKSCAN3, CDC123, C10orf11, LRP1, CCDC38, MMP15, CFDP1 and KCNE2. Identification of these 16 new loci may p…

OncologyVital capacityPROTEINGenome-wide association studyBLOOD-PRESSUREVARIANTSPulmonary function testingPulmonary Disease Chronic Obstructive0302 clinical medicineEpidemiologyIMPUTATIONChild11 Medical and Health SciencesPOPULATIONGenetics & HeredityRISK0303 health scienceseducation.field_of_studyWOMENGENETIC-VARIATION3. Good healthRespiratory Function Testsmedicine.anatomical_structureMedical geneticsLife Sciences & BiomedicineEXPRESSIONmedicine.medical_specialtyMECOMPopulationEuropean Continental Ancestry GroupBiologyOBSTRUCTIVE PULMONARY-DISEASEArticleWhite People03 medical and health sciencesInternal medicineGeneticsmedicineHumanseducationMETAANALYSISPOLYMORPHISMS030304 developmental biologyLungScience & TechnologyMORTALITYGIANT consortiumInternational Lung Cancer Consortium06 Biological Sciences030228 respiratory systemImmunologylung; gene; gwasGenome-Wide Association StudyDevelopmental BiologyNature Genetics
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Large-scale association analysis identifies new risk loci for coronary artery disease

2016

Coronary artery disease (CAD) is the commonest cause of death. Here, we report an association analysis in 63,746 CAD cases and 130,681 controls identifying 15 loci reaching genome-wide significance, taking the number of susceptibility loci for CAD to 46, and a further 104 independent variants (r 2 < 0.2) strongly associated with CAD at a 5% false discovery rate (FDR). Together, these variants explain approximately 10.6% of CAD heritability. Of the 46 genome-wide significant lead SNPs, 12 show a significant association with a lipid trait, and 5 show a significant association with blood pressure, but none is significantly associated with diabetes. Network analysis with 233 candidate genes …

AdultAsian Continental Ancestry GroupMaleCandidate geneBIO/12 - BIOCHIMICA CLINICA E BIOLOGIA MOLECOLARE CLINICAPopulationEuropean Continental Ancestry GroupQuantitative Trait LociCADGenome-wide association studySingle-nucleotide polymorphismCoronary Artery Disease030204 cardiovascular system & hematologyBiologyQuantitative trait locusBioinformaticsPolymorphism Single NucleotideArticleWhite Peoplecoronary artery disease risk lociCell LineCoronary artery disease03 medical and health sciences0302 clinical medicineAsian PeopleRisk FactorsmedicineHumansgeneticsGene Regulatory NetworksGenetic Predisposition to Diseasecardiovascular diseasesPolymorphismeducation030304 developmental biologyGenetic associationAgedGenetics0303 health scienceseducation.field_of_studyAdult Aged Asian Continental Ancestry Group Cell Line Coronary Artery Disease; genetics European Continental Ancestry Group; genetics Female Gene Regulatory Networks Genetic Predisposition to Disease Genome-Wide Association Study Humans Male Middle Aged Polymorphism; Single Nucleotide Quantitative Trait Loci Risk FactorsSingle NucleotideMiddle Agedmedicine.disease3. Good healthFemaleGenome-Wide Association StudyNature Genetics
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Genetic associations at 53 loci highlight cell types and biological pathways relevant for kidney function

2016

Reduced glomerular filtration rate defines chronic kidney disease and is associated with cardiovascular and all-cause mortality. We conducted a meta-analysis of genome-wide association studies for estimated glomerular filtration rate (eGFR), combining data across 133,413 individuals with replication in up to 42,166 individuals. We identify 24 new and confirm 29 previously identified loci. Of these 53 loci, 19 associate with eGFR among individuals with diabetes. Using bioinformatics, we show that identified genes at eGFR loci are enriched for expression in kidney tissues and in pathways relevant for kidney development and transmembrane transporter activity, kidney structure, and regulation o…

0301 basic medicineNephrologyGenetics and Molecular Biology (all)estimated glomerular filtration rateestimated glomerular filtration rate chronic kidney disease genetic determinantsGeneral Physics and AstronomyKidney developmentGenome-wide association studyBiochemistrySettore MED/14 - NEFROLOGIARenal InsufficiencyChronicGeneticsAGEN Consortiumddc:616education.field_of_studyKidneyStage renal-diseaseMultidisciplinaryGenome-wide associationCHARGe-Heart Failure GroupGene Expression Regulation; Genome-Wide Association Study; Genotype; Humans; Renal Insufficiency Chronic; Genetic Predisposition to Disease; Biochemistry Genetics and Molecular Biology (all); Chemistry (all); Physics and Astronomy (all)QChemistry (all)MetaanalysisGene Expression Regulation; Genetic Predisposition to Disease; Genome-Wide Association Study; Genotype; Humans; Renal Insufficiency Chronic/geneticsBiological sciencesSerum creatininemedicine.anatomical_structureEfficientRonyons -- FisiologiaHypertensionICBP ConsortiumTransmembrane transporter activitygenetic association loci kidney functionCARDIOGRAMHumanmedicine.medical_specialtyGenotypeSciencePopulationRenal functionECHOGen ConsortiumReplicationBiologyEnvironmentResearch SupportGeneral Biochemistry Genetics and Molecular BiologyN.I.H.genetic determinants03 medical and health sciencesPhysics and Astronomy (all)GENOME-WIDE ASSOCIATION ; FALSE DISCOVERY RATES ; STAGE RENAL-DISEASE ; SERUM CREATININE ; METAANALYSIS ; VARIANTS ; INDIVIDUALS ; POPULATION ; RISK ; HYPERTENSIONKidney functionResearch Support N.I.H. ExtramuralInternal medicineMD MultidisciplinarymedicineGeneticsJournal ArticleHumanseGFRcrea; eGFRcysGenetic Predisposition to Diseaseddc:610GenetikRenal Insufficiency ChronicMortalityeducationddc:613Biochemistry Genetics and Molecular Biology (all)urogenital systemIndividualsExtramuralGeneral Chemistryta3121medicine.diseaseR1030104 developmental biologyGene Expression RegulationBiochemistry Genetics and Molecular Biology (all); Chemistry (all); Physics and Astronomy (all)570 Life sciences; biologyGenèticachronic kidney diseaseKidney diseaseGenome-Wide Association StudyMeta-Analysis
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New loci associated with kidney function and chronic kidney disease

2010

Chronic kidney disease (CKD) is a significant public health problem, and recent genetic studies have identified common CKD susceptibility variants. The CKDGen consortium performed a meta-analysis of genome-wide association data in 67,093 individuals of European ancestry from 20 predominantly population-based studies in order to identify new susceptibility loci for reduced renal function as estimated by serum creatinine (eGFRcrea), serum cystatin c (eGFRcys) and CKD (eGFRcrea 60 ml/min/1.73 m 2; n = 5,807 individuals with CKD (cases)). Follow-up of the 23 new genome-wide-significant loci (P 5 × 10 8) in 22,982 replication samples identified 13 new loci affecting renal function and CKD (in or…

medicine.medical_specialtyGENOME-WIDE ASSOCIATION ; SERUM CREATININE ; PROTEIN ; GENE ; MUTATIONS ; VARIANTS ; POPULATION ; CANDIDATE ; HOMOLOG ; MEGALINPopulationRenal functionGenome-wide association studyBiologyKidneyurologic and male genital diseasesCohort Studieschemistry.chemical_compoundSDG 3 - Good Health and Well-beingRisk FactorsInternal medicineGenetic MarkermedicineGeneticsHumansCystatin CeducationCystatin C/geneticsddc:616Genetic Markers/geneticsCreatinineKidneyeducation.field_of_studyModels GeneticRisk Factorchronic kidney disease; loci; SNPCreatinine/bloodmedicine.diseaseDietEuropeKidney/*physiologyEndocrinologymedicine.anatomical_structurechemistryCystatin CRenal physiologyCreatininebiology.proteinKidney Failure ChronicKidney Failure Chronic/ethnology/*geneticsCohort StudieKidney diseaseHumanGenome-Wide Association StudyGlomerular Filtration Rate
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