0000000000419765

AUTHOR

Nicholas L. Smith

showing 9 related works from this author

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
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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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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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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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A meta-analysis of 120 246 individuals identifies 18 new loci for fibrinogen concentration

2015

Genome-wide association studies have previously identified 23 genetic loci associated with circulating fibrinogen concentration. These studies used HapMap imputation and did not examine the X-chromosome. 1000 Genomes imputation provides better coverage of uncommon variants, and includes indels. We conducted a genome-wide association analysis of 34 studies imputed to the 1000 Genomes Project reference panel and including similar to 120 000 participants of European ancestry (95 806 participants with data on the X-chromosome). Approximately 10.7 million single-nucleotide polymorphisms and 1.2 million indels were examined. We identified 41 genome-wide significant fibrinogen loci ; of which, 18 …

AdultMale0301 basic medicineNetherlands Twin Register (NTR)Single-nucleotide polymorphismGenome-wide association studyBiologyPolymorphism Single NucleotideWhite People03 medical and health sciencesINDEL MutationGenetics/dk/atira/pure/keywords/cohort_studies/netherlands_twin_register_ntr_Humans1000 Genomes ProjectInternational HapMap ProjectIndelMolecular BiologyGenetics (clinical)ComputingMilieux_MISCELLANEOUSAgedGenetic associationAged 80 and overGeneticsAssociation Studies ArticlesFibrinogen[SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/HematologyGeneral MedicineMiddle AgedGenetic architecture030104 developmental biologyGenetic LociFemaleGENOME-WIDE ASSOCIATION ; C-REACTIVE PROTEIN ; CARDIOVASCULAR-DISEASE ; CIRCULATING FIBRINOGEN ; GENETIC ARCHITECTURE ; VARIANTS ; DESIGN ; HEMOSTASIS ; RESOURCE ; HEALTHImputation (genetics)Genome-Wide Association Study
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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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Genome-Wide Association Study for Incident Myocardial Infarction and Coronary Heart Disease in Prospective Cohort Studies: The CHARGE Consortium

2016

Background Data are limited on genome-wide association studies (GWAS) for incident coronary heart disease (CHD). Moreover, it is not known whether genetic variants identified to date also associate with risk of CHD in a prospective setting. Methods We performed a two-stage GWAS analysis of incident myocardial infarction (MI) and CHD in a total of 64,297 individuals (including 3898 MI cases, 5465 CHD cases). SNPs that passed an arbitrary threshold of 5×10−6 in Stage I were taken to Stage II for further discovery. Furthermore, in an analysis of prognosis, we studied whether known SNPs from former GWAS were associated with total mortality in individuals who experienced MI during follow-up. Res…

Male0301 basic medicineOncologyPREDICTIONMyocardial Infarctionlcsh:MedicineGenome-wide association studyCoronary Artery DiseaseCardiovascular MedicineSUSCEPTIBILITY030204 cardiovascular system & hematologyCardiovascularBioinformaticsincident myocardial infarctionCohort StudiesCoronary artery diseaseMathematical and Statistical Techniques0302 clinical medicineDESIGNMedicine and Health Sciences2.1 Biological and endogenous factorsProspective StudiesMyocardial infarctionAetiologyCooperative Behaviorlcsh:ScienceProspective cohort studyRISKscreening and diagnosisMultidisciplinaryResearch Support Non-U.S. Gov'tSingle NucleotideGenomicsMiddle Aged3. Good healthMultidisciplinary SciencesDetectionCHROMOSOME 9P21Heart DiseaseResearch DesignCardiovascular DiseasesCARDIOVASCULAR-DISEASEPhysical SciencesScience & Technology - Other TopicsFemaleStatistics (Mathematics)4.2 Evaluation of markers and technologiesResearch ArticleCohort studymedicine.medical_specialtyGeneral Science & TechnologyCardiologySingle-nucleotide polymorphismResearch and Analysis MethodsGenome ComplexityPolymorphism Single Nucleotide03 medical and health sciencescoronary hearth diseaseInternal medicineMD MultidisciplinaryGenome-Wide Association StudiesGeneticsJournal ArticlemedicineHumansSNPGenetic Predisposition to DiseasePolymorphismStatistical MethodsHeart Disease - Coronary Heart DiseaseMETAANALYSISAgedGenetic associationta112Science & Technologybusiness.industryPreventionlcsh:RHuman GenomeBiology and Life SciencesComputational BiologyHuman GeneticsGenome AnalysisROTTERDAMmedicine.diseaseIntronsGood Health and Well Being030104 developmental biologyGenetic LociGenetics of Diseaselcsh:Q3111 BiomedicinebusinessMathematicsMeta-AnalysisGenome-Wide Association StudyPLOS ONE
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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 >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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