0000000000088135

AUTHOR

David S. Siscovick

showing 11 related works from this author

New susceptibility locus for coronary artery disease on chromosome 3q22.3

2009

We present a three-stage analysis of genome-wide SNP data in 1,222 German individuals with myocardial infarction and 1,298 controls, in silico replication in three additional genome-wide datasets of coronary artery disease (CAD) and subsequent replication in approximately 25,000 subjects. We identified one new CAD risk locus on 3q22.3 in MRAS (P = 7.44 x 10(-13); OR = 1.15, 95% CI = 1.11-1.19), and suggestive association with a locus on 12q24.31 near HNF1A-C12orf43 (P = 4.81 x 10(-7); OR = 1.08, 95% CI = 1.05-1.11).

medicine.medical_specialtyQuantitative Trait LociLocus (genetics)Single-nucleotide polymorphismGenome-wide association studyCoronary Artery DiseaseQuantitative trait locusBiologyBioinformaticsPolymorphism Single NucleotideArticleCoronary artery diseaseGermanyInternal medicineGeneticsmedicineHumansGenetic Predisposition to DiseaseHepatocyte Nuclear Factor 1-alphaMyocardial infarctionCase-control studyChromosomemedicine.diseaseCase-Control Studiesras ProteinsCardiologyChromosomes Human Pair 3Genome-Wide Association Study
researchProduct

Genome-wide association analyses identify multiple loci associated with central corneal thickness and keratoconus

2013

The author manuscript of this article is open access and is freely available online at PubMed Central

medicine.medical_specialtyKeratoconusCorneal Pachymetrygenetic structuresthickness; keratoconus; geneGlaucomaOcular hypertensionGenome-wide association studyBiologyReal-Time Polymerase Chain ReactionKeratoconusWhite PeopleArticleCentral corneal thicknessCorneaAsian PeopleOphthalmologyCorneaOdds RatioGeneticsmedicineHumansCorneal pachymetrymedicine.diagnostic_testForkhead Box Protein O1Forkhead Transcription FactorsGlaucomaOdds ratioMicroarray Analysismedicine.diseaseConfidence intervaleye diseasesFibronectinsmedicine.anatomical_structureGenetic Locisense organsGenome-Wide Association Study
researchProduct

Large-Scale Gene-Centric Meta-Analysis across 39 Studies Identifies Type 2 Diabetes Loci

2012

To identify genetic factors contributing to type 2 diabetes (T2D), we performed large-scale meta-analyses by using a custom ∼50,000 SNP genotyping array (the ITMAT-Broad-CARe array) with ∼2000 candidate genes in 39 multiethnic population-based studies, case-control studies, and clinical trials totaling 17,418 cases and 70,298 controls. First, meta-analysis of 25 studies comprising 14,073 cases and 57,489 controls of European descent confirmed eight established T2D loci at genome-wide significance. In silico follow-up analysis of putative association signals found in independent genome-wide association studies (including 8,130 cases and 38,987 controls) performed by the DIAGRAM consortium id…

AdultMaleCandidate geneSNP ARRAYAdolescentGenotypeSUSCEPTIBILITY LOCI030209 endocrinology & metabolismGenome-wide association studySingle-nucleotide polymorphismLocus (genetics)BLOOD-PRESSUREBiologyPolymorphism Single NucleotideArticleYoung Adult03 medical and health sciences0302 clinical medicineEthnicityGeneticsHumansEUROPEAN AMERICANSGenetic Predisposition to DiseaseRESOURCE CAREGenetics(clinical)GENOME-WIDE ASSOCIATIONGenetics (clinical)Aged030304 developmental biologyGenetic associationAged 80 and overGeneticsAFRICAN-AMERICANS0303 health sciencesINSULIN-RESISTANCECOMMON VARIANTSMiddle Aged3. Good healthSNP genotypingDiabetes Mellitus Type 2Genetic LociCase-Control StudiesRISK-FACTORSFemaleTCF7L2Follow-Up StudiesGenome-Wide Association StudySNP array
researchProduct

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
researchProduct

Genome-Wide Association Study of the Modified Stumvoll Insulin Sensitivity Index Identifies BCL2 and FAM19A2 as Novel Insulin Sensitivity Loci.

2016

Genome-wide association studies (GWAS) have found few common variants that influence fasting measures of insulin sensitivity. We hypothesized that a GWAS of an integrated assessment of fasting and dynamic measures of insulin sensitivity would detect novel common variants. We performed a GWAS of the modified Stumvoll Insulin Sensitivity Index (ISI) within the Meta-Analyses of Glucose and Insulin-Related Traits Consortium. Discovery for genetic association was performed in 16,753 individuals, and replication was attempted for the 23 most significant novel loci in 13,354 independent individuals. Association with ISI was tested in models adjusted for age, sex, and BMI and in a model analyzing t…

0301 basic medicineMaleInsulin Receptor Substrate ProteinsEndocrinology Diabetes and MetabolismLocus (genetics)Genome-wide association studyPolymorphism Single Nucleotide03 medical and health sciencesEndocrinology & MetabolismInsulin resistanceGenotypeInternal MedicinemedicineHumansGenetic Predisposition to DiseaseGenetic associationGeneticsbusiness.industryInsulin sensitivityGenetics/Genomes/Proteomics/Metabolomics11 Medical And Health Sciencesmedicine.diseaseIRS1030104 developmental biologyProto-Oncogene Proteins c-bcl-2Chemokines CCInsulin Receptor Substrate ProteinsFemaleInsulin ResistancebusinessGenome-Wide Association Study
researchProduct

Genome-wide Association Studies Identify Genetic Loci Associated with Albuminuria in Diabetes

2016

Elevated concentrations of albumin in the urine, albuminuria, are a hallmark of diabetic kidney disease and are associated with an increased risk for end-stage renal disease and cardiovascular events. To gain insight into the pathophysiological mechanisms underlying albuminuria, we conducted meta-analyses of genome-wide association studies and independent replication in up to 5,825 individuals of European ancestry with diabetes and up to 46,061 without diabetes, followed by functional studies. Known associations of variants in CUBN, encoding cubilin, with the urinary albumin-to-creatinine ratio (UACR) were confirmed in the overall sample (P = 2.4 × 10−10). Gene-by-diabetes interactions were…

Male0301 basic medicinediabetes geneEndocrinology Diabetes and MetabolismGenome-wide association studyKidneyGLOMERULAR-FILTRATION-RATECathepsin CGene Knockout TechniquescubilinSettore MED/14 - NEFROLOGIADiabetic NephropathiesMODULATES PROTEINURIAddc:616HERITABILITYDiabetesGenetics/Genomes/Proteomics/MetabolomicsMiddle AgedRISK POPULATION COHORTS3. Good healthINSIGHTSKidney TubulesFemaleSulfotransferasesmedicine.symptomRAB38AdultEXPRESSIONmedicine.medical_specialtyRenal functionReceptors Cell Surface610 Medicine & healthSingle-nucleotide polymorphismBiologyPolymorphism Single NucleotidealbuminuriaDiabetes Mellitus Experimental03 medical and health sciencesDiabetes mellitusInternal medicineInternal MedicinemedicineAnimalsHumansGenetic Predisposition to DiseaseAgedMORTALITYKIDNEY-DISEASEmedicine.diseaseCubilinRatsMinor allele frequency030104 developmental biologyEndocrinologyDiabetes Mellitus Type 2rab GTP-Binding ProteinsCOLLABORATIVE METAANALYSISAlbuminuria570 Life sciences; biologyalbuminuria diabetes cubilinGenome-Wide Association StudyKidney disease
researchProduct

Plasma HDL cholesterol and risk of myocardial infarction: a mendelian randomisation study

2012

BACKGROUND: High plasma HDL cholesterol is associated with reduced risk of myocardial infarction, but whether this association is causal is unclear. Exploiting the fact that genotypes are randomly assigned at meiosis, are independent of non-genetic confounding, and are unmodified by disease processes, mendelian randomisation can be used to test the hypothesis that the association of a plasma biomarker with disease is causal. METHODS: We performed two mendelian randomisation analyses. First, we used as an instrument a single nucleotide polymorphism (SNP) in the endothelial lipase gene (LIPG Asn396Ser) and tested this SNP in 20 studies (20,913 myocardial infarction cases, 95,407 controls). Se…

LOCIMyocardial Infarction030204 cardiovascular system & hematologychemistry.chemical_compound0302 clinical medicineHigh-density lipoproteinGene Frequencyplasma HDL cholesterol ; mendelian randomisation ; MIHDL cholesterolsingle nucleotide polymorphismRisk FactorsGENETIC-VARIANTSARTERY-DISEASEProspective StudiesMyocardial infarction0303 health sciencesHDL cholesterol; myocardial infarction; single nucleotide polymorphismISCHEMIC CARDIOVASCULAR-DISEASEGeneral Medicine3. Good healthCardiologylipids (amino acids peptides and proteins)medicine.medical_specialtyDalcetrapibSingle-nucleotide polymorphismPolymorphism Single Nucleotide03 medical and health sciencesInternal medicinemedicineHumansCORONARY-HEART-DISEASEGenetic Predisposition to DiseaseMETAANALYSIS030304 developmental biologyBLOOD CHOLESTEROLbusiness.industryCholesterolCholesterol HDLCase-control studyCholesterol LDLLipaseOdds ratioMendelian Randomization Analysismedicine.diseaseENDOTHELIAL LIPASEATHEROSCLEROSISchemistryCase-Control StudiesbusinessHIGH-DENSITY-LIPOPROTEINBiomarkersEvacetrapibThe Lancet
researchProduct

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
researchProduct

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
researchProduct

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
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