0000000000429261

AUTHOR

Martin G. Larson

showing 14 related works from this author

Trajectories of Blood Pressure Elevation Preceding Hypertension Onset: An Analysis of the Framingham Heart Study Original Cohort

2018

Importance Given that hypertension remains a leading risk factor for chronic disease globally, there are substantial ongoing efforts to define the optimal range of blood pressure (BP). Objective To identify a common threshold level above which BP rise tends to accelerate in progression toward hypertension. Design, Setting, and Participants This longitudinal, community-based epidemiological cohort study of adults enrolled in Framingham, Massachusetts, included 1252 participants (mean [SD] age, 35.3 [2.7] years) from the Framingham Original Cohort, of whom 790 (63.1%) were women. Each participant contributed up to 28 serial examinations of standardized resting BP measurements between 1948 and…

AdultMalemedicine.medical_specialtysystolic blood pressuresegmented mixed modelHemodynamicsBlood Pressurethreshold value030204 cardiovascular system & hematology03 medical and health sciencesSex Factors0302 clinical medicineFramingham Heart StudyInternal medicineHumansMedicineLongitudinal Studies030212 general & internal medicineAge of OnsetRisk factorAgedAged 80 and overFramingham Risk Scorebusiness.industryBrief ReportAge FactorsMiddle Agedta3121Blood pressureMassachusettsHypertensionCohortDisease ProgressionCardiologyFemaleAge of onsetCardiology and Cardiovascular MedicinebusinessCohort study
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Genetic variants associated with cardiac structure and function: a meta-analysis and replication of genome-wide association data.

2009

Context Echocardiographic measures of left ventricular (LV) structure and function are heritable phenotypes of cardiovascular disease. Objective To identify common genetic variants associated with cardiac structure and function by conducting a meta-analysis of genome-wide association data in 5 population-based cohort studies (stage 1) with replication (stage 2) in 2 other community-based samples. Design, Setting, and Participants Within each of 5 community-based cohorts comprising the EchoGen consortium (stage 1; n = 12 612 individuals of European ancestry; 55% women, aged 26-95 years; examinations between 1978-2008), we estimated the association between approximately 2.5 million single-nuc…

AdultMalemedicine.medical_specialtyPathologyGenotypeHeart VentriclesPopulationLocus (genetics)Genome-wide association studySingle-nucleotide polymorphismPolymorphism Single NucleotideVentricular Function LeftWhite PeopleArticleVentricular Dysfunction LeftSDG 3 - Good Health and Well-beingRisk FactorsInternal medicineMedicineHumansHeart AtriaInternational HapMap ProjecteducationAortaAgedAged 80 and overeducation.field_of_studybusiness.industryGeneral MedicineOrgan SizeMiddle AgedPhenotypeCardiovascular DiseasesEchocardiographyMeta-analysisCohortCardiologyFemalebusinessCohort studyGenome-Wide Association StudyJAMA
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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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Relation of Multiple Inflammatory Biomarkers to Incident Atrial Fibrillation

2009

Basic and clinical studies have suggested that inflammation predisposes to atrial fibrillation (AF). We assessed the association of 12 circulating inflammatory biomarkers (i.e., C-reactive protein, fibrinogen, interleukin-6, intercellular adhesion molecule-1, lipoprotein-associated phospholipase A2 [mass and activity], monocyte chemoattractant protein-1, myeloperoxidase, CD40 ligand, osteoprotegerin, P-selectin, and tumor necrosis factor receptor II) with incident AF in 2863 Framingham Offspring Study participants (mean age 60.7 years, SD = 9.4, 55% women). During follow-up (median 6 years), 148 participants (43% women) developed incident AF. In the multivariable proportional hazards models…

Malemedicine.medical_specialtyHeart diseaseArticleOsteoprotegerinRisk FactorsInternal medicineGermanyAtrial FibrillationConfidence IntervalsOdds RatioMedicineHumansMyocardial infarctionProspective StudiesInflammationFramingham Risk Scorebusiness.industryProportional hazards modelIncidenceHazard ratioOsteoprotegerinAtrial fibrillationMiddle Agedmedicine.diseaseSurvival AnalysisConfidence intervalC-Reactive ProteinMultivariate AnalysisCardiologyFemaleCardiology and Cardiovascular MedicinebusinessBiomarkers
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Clinical correlates of change in inflammatory biomarkers: The Framingham Heart Study

2013

Objectives: Traditional clinical risk factors are associated with inflammation cross-sectionally, but associations of longitudinal variation in inflammatory biomarkers with corresponding changes in clinical risk factors are incompletely described. We sought to analyze clinical factors associated with change in inflammation in the community.Methods: We studied 3013 Framingham Offspring (n = 2735) and Omni Cohort (n = 278) participants (mean age 59 years, 55% women, 9% ethnic/racial minority) who attended two consecutive examination cycles (mean 6.7 years apart). We selected ten inflammatory biomarkers representing distinctive biological functions: C-reactive protein (CRP), intercellular adhe…

OncologyMaleBLOOD-PRESSUREIsoprostanesFramingham Heart StudyRisk FactorsMyocardial infarctionOXIDATIVE STRESSskin and connective tissue diseasesChemokine CCL2Biological markersbiologyLongitudinal studiesMiddle AgedIntercellular Adhesion Molecule-1Inflammatory biomarkersC-REACTIVE PROTEINP-SelectinADIPOSE-TISSUEMassachusettsCardiovascular DiseasesCARDIOVASCULAR-DISEASEFemalemedicine.symptomCardiology and Cardiovascular MedicineVasculitisVasculitismedicine.medical_specialtyInflammationArticleInternal medicinemedicineHumansReceptors Tumor Necrosis Factor Type IIInterleukin 6AgedInflammationbusiness.industryInterleukin-6PERIPHERAL ARTERIAL-DISEASEC-reactive proteinOsteoprotegerinADHESION MOLECULE-1medicine.diseasePHOSPHOLIPASE A(2)Blood pressurePLASMA-CONCENTRATIONMYOCARDIAL-INFARCTIONImmunology1-Alkyl-2-acetylglycerophosphocholine Esterasebiology.proteinsense organsbusinessBiomarkers
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Lipidomic profiling identifies signatures of metabolic risk

2020

Background: Metabolic syndrome (MetS), the clustering of metabolic risk factors, is associated with cardiovascular disease risk. We sought to determine if dysregulation of the lipidome may contribute to metabolic risk factors. Methods: We measured 154 circulating lipid species in 658 participants from the Framingham Heart Study (FHS) using liquid chromatography-tandem mass spectrometry and tested for associations with obesity, dysglycemia, and dyslipidemia. Independent external validation was sought in three independent cohorts. Follow-up data from the FHS were used to test for lipid metabolites associated with longitudinal changes in metabolic risk factors. Results: Thirty-nine lipids were…

Male0301 basic medicineResearch paperdhSL dihydrosphingolipidBMI body mass indexlcsh:MedicineATHEROGENIC LIPOPROTEINSBioinformaticsFHS Framingham Heart StudyPC phosphatidylcholinePESA Progression of Early Subclinical Atherosclerosis0302 clinical medicineFramingham Heart StudyRisk FactorsSAFHS San Antonio Family Heart StudyLC-MS/MS liquid chromatography-tandem mass spectrometryMedicineLongitudinal StudiesMetabolic riskPLASMA SPHINGOLIPID METABOLISMPOPULATIONlcsh:R5-920education.field_of_studySPHINGOMYELINCE cholesteryl esterDysglycemiaGeneral MedicineMiddle AgedLipidomePS phosphatidylserineCardiovascular diseaseLipidsMetabolic syndrome3. Good healthCARDIOVASCULAR-DISEASE030220 oncology & carcinogenesisHEARTMetS metabolic syndromeFemaleDisease SusceptibilityLGPL lysoglycerophospholipidSL sphingolipidlcsh:Medicine (General)LPE lysophosphatidylethanolamineAdultFDR false discovery rateTAG triacylglycerolPopulationCer ceramideCVD cardiovascular diseasePE phosphatidylethanolamineDENSITY-LIPOPROTEINRisk AssessmentGeneral Biochemistry Genetics and Molecular Biology03 medical and health sciencesAnimalsHumanseducationT2DM type II diabetes mellitusAgedLPC lysophosphatidylcholineSM sphingomyelinbusiness.industryCERAMIDElcsh:RHDL-C High density lipoprotein cholesterolBiomarkerLipid Metabolismmedicine.diseaseObesitySphingolipidCross-Sectional Studies030104 developmental biologyDyslipidemiaERF Erasmus Family StudyLipidomicsMetabolic syndromeINDUCED INSULIN-RESISTANCEbusinessDAG diacylglycerolBody mass indexBiomarkersDyslipidemiaMRM multiple reaction monitoringFASTING GLUCOSE
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Variants in ZFHX3 are associated with atrial fibrillation in individuals of European ancestry

2009

We conducted meta-analyses of genome-wide association studies (GWAS) for atrial fibrillation (AF) in participants from five community-based cohorts. Meta-analyses of 896 prevalent (15,768 referents) and 2,517 incident (21,337 referents) AF cases identified a novel locus for AF (ZFHX3, rs2106261, risk ratio [RR]=1.19; P=2.3×10−7), an association that was replicated in the German AF Network (odds ratio=1.44; P=1.6×10−11). Combining the discovery and replication results, rs2106261 was significantly associated with AF (RR=1.25; P=1.8×10−15).

single nucleotideEuropean Continental Ancestry Group/*geneticsmedicine.medical_specialtyMutation/*geneticsGenome-wide association study030204 cardiovascular system & hematologyBiologyPolymorphism Single NucleotideArticleWhite PeoplepolymorphismHomeodomain Proteins/*genetics03 medical and health sciences0302 clinical medicineMeta-Analysis as TopicInternal medicineAtrial FibrillationGeneticsmedicineHumansGenetic Predisposition to Disease030304 developmental biologyGenetic associationHomeodomain Proteinsddc:6160303 health sciencesAtrial Fibrillation/*geneticsReproducibility of ResultsAtrial fibrillationOdds ratioPolymorphism Single Nucleotide/geneticsmedicine.disease*Genetic Predisposition to DiseaseMeta-analysisRelative riskMutationCohortepidemiologyChromosomes Human Pair 16/geneticsChromosomes Human Pair 16Genome-Wide Association StudyNature Genetics
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Genome-wide association study of PR interval.

2009

The electrocardiographic PR interval reflects atrial and atrioventricular nodal conduction, disturbances of which increase risk of atrial fibrillation (AF). To identify underlying common genetic variation, we meta-analyzed genome-wide association results for PR interval from seven community-based studies of European-ancestry individuals in the CHARGE consortium: AGES, ARIC, CHS, FHS, KORA, Rotterdam Study, and SardiNIA (N=28,517). Statistically significant loci (P<5×10-8) were tested for association with AF (N=5,741 cases). We identified nine loci associated with PR interval. At chromosome 3p22.2, we observed two independent associations in voltage gated sodium channel genes SCN10A and SCN5…

MaleCandidate genePopulationvoltage gated sodium channelGenome-wide association studyLocus (genetics)030204 cardiovascular system & hematologyBiologyArticleCohort Studiesquantitative trait03 medical and health sciencesRotterdam StudyElectrocardiography0302 clinical medicineMeta-Analysis as TopicHeart Conduction SystemAtrial FibrillationGeneticsmedicineHumansGenetic Predisposition to Diseasecardiovascular diseasesPR intervaleducation030304 developmental biologyGenetic associationAgedGeneticsdevelopmental genes0303 health scienceseducation.field_of_studygenome-wide association studyPQ intervalAtrial fibrillationmedicine.diseaseGenetic Locicardiovascular systemPR intervalFemaleNature genetics
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Common Genetic Variation in Relation to Brachial Vascular Dimensions and Flow-Mediated Vasodilation

2019

Common Genetic Variation in Relation to Brachial Vascular Dimensions and Flow-Mediated Vasodilation

Malemedicine.medical_specialtyBrachial ArteryVasodilationGenome-wide association studyPolymorphism Single NucleotideArticleInternal medicinemedicine.arteryGenetic variationmedicineHumanscardiovascular diseasesBrachial arteryCation Transport ProteinsUltrasonographybusiness.industryGenetic VariationGeneral MedicineMethyltransferasesta3121Middle Agedbody regionsVasodilationInsulin-Like Growth Factor Binding Protein 3PhenotypeCardiovascular DiseasesGenetic Locicardiovascular systemCardiologyMedical geneticsDilation (morphology)Femalebusinesscirculatory and respiratory physiologyFlow-Mediated Vasodilation
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Joint associations of accelerometer-measured physical activity and sedentary time with all-cause mortality: a harmonised meta-analysis in more than 4…

2020

Funder: National Institute for Health Research (NIHR) Collaboration for Leadership in Applied Health Research and Care East Midlands

Time Factors2314educationPhysical activityPhysical Therapy Sports Therapy and RehabilitationsedentarydeathAccelerometryCox proportional hazards regressionHumansMedicineOrthopedics and Sports Medicine1506Prospective cohort study1507Exercisehealth care economics and organizationsAgedSedentary timeMortality Prematurebusiness.industryOriginal researchMortality rateGeneral MedicineMiddle AgedVDP::Medisinske Fag: 700::Idrettsmedisinske fag: 850Peer reviewmeta-analysisaccelerometerMeta-analysisSedentary BehaviorbusinessAll cause mortalityDemographyBritish Journal of Sports Medicine
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Large-scale genome-wide analysis identifies genetic variants associated with cardiac structure and function

2017

BACKGROUND: Understanding the genetic architecture of cardiac structure and function may help to prevent and treat heart disease. This investigation sought to identify common genetic variations associated with inter-individual variability in cardiac structure and function. METHODS: A GWAS meta-analysis of echocardiographic traits was performed, including 46,533 individuals from 30 studies (EchoGen consortium). The analysis included 16 traits of left ventricular (LV) structure, and systolic and diastolic function. RESULTS: The discovery analysis included 21 cohorts for structural and systolic function traits (n = 32,212) and 17 cohorts for diastolic function traits (n = 21,852). Replication …

0301 basic medicineMaleGenome-wide association studyBLOOD-PRESSUREResearch & Experimental Medicine030204 cardiovascular system & hematologyCoronary artery diseasegenome-wide0302 clinical medicineEPIDEMIOLOGYMyocardial infarctionGeneticsRISK11 Medical And Health SciencesGeneral Medicine3. Good healthMedicine Research & Experimentalcardiovascular systemMedical geneticsCORONARY-ARTERY-DISEASEHEART-FAILUREFemaleLife Sciences & Biomedicinemedicine.medical_specialtyHeart DiseasesImmunologyQuantitative trait locusPolymorphism Single Nucleotide03 medical and health sciencesQuantitative Trait HeritableGenetic variationmedicineHumansMETAANALYSISScience & Technologybusiness.industryMyocardiumta3121medicine.diseaseGenetic architecture030104 developmental biologyMYOCARDIAL-INFARCTIONGenetic LociHeart failureREPLICATIONClinical MedicinebusinessREDUCED EJECTION FRACTIONSUPPRESSOR GENEGenome-Wide Association Study
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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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Meta-Analysis of Genome-Wide Association Studies in &gt;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
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Association of Common Variants in NPPA and NPPB with Circulating Natriuretic Peptides and Blood Pressure

2009

We examined the association of common variants at the NPPA-NPPB locus with circulating concentrations of the natriuretic peptides, which have blood pressure-lowering properties. We genotyped SNPs at the NPPA-NPPB locus in 14,743 individuals of European ancestry, and identified associations of plasma atrial natriuretic peptide with rs5068 (P = 8 x 10(-70)), rs198358 (P = 8 x 10(-30)) and rs632793 (P = 2 x 10(-10)), and of plasma B-type natriuretic peptide with rs5068 (P = 3 x 10(-12)), rs198358 (P = 1 x 10(-25)) and rs632793 (P = 2 x 10(-68)). In 29,717 individuals, the alleles of rs5068 and rs198358 that showed association with increased circulating natriuretic peptide concentrations were a…

AdultMaleLinkage disequilibriummedicine.medical_specialtymedicine.drug_classHemodynamicsSingle-nucleotide polymorphismBlood PressureBiologyPolymorphism Single NucleotideArticleLinkage DisequilibriumAtrial natriuretic peptideGene FrequencyInternal medicineNatriuretic Peptide BrainGeneticsmedicineNatriuretic peptideHumansGenetic Predisposition to DiseaseAlleleNatriuretic PeptidesAllele frequencyAgedMiddle AgedEndocrinologyBlood pressureCase-Control StudiesHypertensionFemaleAtrial Natriuretic FactorNature genetics
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