0000000000559783

AUTHOR

Kathryn L. Lunetta

showing 16 related works from this author

Genome-wide association studies identify 137 genetic loci for DNA methylation biomarkers of aging

2021

Abstract Background Biological aging estimators derived from DNA methylation data are heritable and correlate with morbidity and mortality. Consequently, identification of genetic and environmental contributors to the variation in these measures in populations has become a major goal in the field. Results Leveraging DNA methylation and SNP data from more than 40,000 individuals, we identify 137 genome-wide significant loci, of which 113 are novel, from genome-wide association study (GWAS) meta-analyses of four epigenetic clocks and epigenetic surrogate markers for granulocyte proportions and plasminogen activator inhibitor 1 levels, respectively. We find evidence for shared genetic loci ass…

AgingMultifactorial InheritanceBLOODEpigenetic clock05 Environmental SciencesbiomarkkeritGenome-wide association studyQH426-470Epigenesis Genetic/dk/atira/pure/core/keywords/icep0302 clinical medicineBiomarkers of agingGWASBiology (General)AdiposityGenetics11832 Microbiology and virology0303 health sciences318 Medical biotechnologyDNA methylation1184 Genetics developmental biology physiologygenomiikkaDna Methylation ; Epigenetic Clock ; Gwasddc:DNA-metylaatioINSIGHTSC-Reactive ProteinepigenetiikkaDNA methylationMENDELIAN RANDOMIZATION/dk/atira/pure/sustainabledevelopmentgoals/good_health_and_well_beingEducational StatusICEPGenetic MarkersPROVIDESSUSCEPTIBILITY LOCIBioinformaticsQH301-705.5GenomicsBiology03 medical and health sciencesNHLBI Trans-Omics for Precision Medicine (TOPMed) ConsortiumAGESDG 3 - Good Health and Well-beingPlasminogen Activator Inhibitor 1REGRESSIONGeneticsHumansEpigeneticsGeneMETAANALYSIS030304 developmental biologyGenome HumanResearchGenetics of DNA Methylation Consortium06 Biological SciencesLipid MetabolismHuman geneticsGenetic architectureImmunity InnateikääntyminenGenetic LociCpG Islands08 Information and Computing Sciences3111 BiomedicineENRICHMENTepigenetic clock030217 neurology & neurosurgeryBiomarkersGenome-Wide Association StudyGranulocytes
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Additional file 4 of Genome-wide association studies identify 137 genetic loci for DNA methylation biomarkers of aging

2021

Additional file 4. Assessment of genomic inflation and heterogeneity.

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Additional file 3 of Genome-wide association studies identify 137 genetic loci for DNA methylation biomarkers of aging

2021

Additional file 3. Supplementary Figures - Figures S1-S31.

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Maternal and fetal genetic effects on birth weight and their relevance to cardio-metabolic risk factors

2019

AbstractBirth weight (BW) variation is influenced by fetal and maternal genetic and non-genetic factors, and has been reproducibly associated with future cardio-metabolic health outcomes. These associations have been proposed to reflect the lifelong consequences of an adverse intrauterine environment. In earlier work, we demonstrated that much of the negative correlation between BW and adult cardio-metabolic traits could instead be attributable to shared genetic effects. However, that work and other previous studies did not systematically distinguish the direct effects of an individual’s own genotype on BW and subsequent disease risk from indirect effects of their mother’s correlated genoty…

MaleNetherlands Twin Register (NTR)LD SCORE REGRESSIONBirth Weight/geneticsPhysiologyGenome-wide association studyBLOOD-PRESSUREBlood PressureType 2 diabetesDISEASEFetal Development0302 clinical medicineModelsPregnancyRisk FactorsGenotypeBirth Weightmaternal genetic030212 general & internal medicineMaternal-Fetal Exchange0303 health sciencesBody Height/genetics1184 Genetics developmental biology physiologyHeart Diseases/etiologySingle NucleotideASSOCIATIONMetabolic Diseases/etiology3. Good healthType 2/etiologyMENDELIAN RANDOMIZATIONGROWTH/dk/atira/pure/sustainabledevelopmentgoals/good_health_and_well_beingFemaleMaternal InheritanceMaternal Inheritance/geneticsAdultBlood Pressure/geneticsHeart DiseasesOffspringBirth weightcardio-metabolic health outcomesBiologyDiabetes Mellitus Type 2/etiologyPolymorphism Single NucleotideArticle03 medical and health sciencesGeneticMetabolic DiseasesSDG 3 - Good Health and Well-beingDiabetes mellitusMendelian randomizationGeneticsmedicineDiabetes Mellitus/dk/atira/pure/keywords/cohort_studies/netherlands_twin_register_ntr_HumansGenetic Predisposition to DiseasePolymorphism030304 developmental biologyGlycemicPregnancyFetusIDENTIFICATIONModels GeneticInfant NewbornInfantbirth weightDIABETES-MELLITUSmedicine.diseaseNewbornFetal Development/geneticsBody HeightMaternal-Fetal Exchange/geneticsLIFEBlood pressureDiabetes Mellitus Type 2ORIGINSInstitut für Ernährungswissenschaft030217 neurology & neurosurgeryGenome-Wide Association Study
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Additional file 6 of Genome-wide association studies identify 137 genetic loci for DNA methylation biomarkers of aging

2021

Additional file 6. Review history.

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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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Additional file 5 of Genome-wide association studies identify 137 genetic loci for DNA methylation biomarkers of aging

2021

Additional file 5. Colocalization plots.

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Additional file 1 of Genome-wide association studies identify 137 genetic loci for DNA methylation biomarkers of aging

2021

Additional file 1. Individual cohort descriptions and acknowledgements.

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Additional file 5 of Genome-wide association studies identify 137 genetic loci for DNA methylation biomarkers of aging

2021

Additional file 5. Colocalization plots.

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Rare coding variants in PLCG2, ABI3, and TREM2 implicate microglial-mediated innate immunity in Alzheimer's disease

2017

International audience; We identified rare coding variants associated with Alzheimer's disease in a three-stage case-control study of 85,133 subjects. In stage 1, we genotyped 34,174 samples using a whole-exome microarray. In stage 2, we tested associated variants (P < 1 × 10-4) in 35,962 independent samples using de novo genotyping and imputed genotypes. In stage 3, we used an additional 14,997 samples to test the most significant stage 2 associations (P < 5 × 10-8) using imputed genotypes. We observed three new genome-wide significant nonsynonymous variants associated with Alzheimer's disease: a protective variant in PLCG2 (rs72824905: p.Pro522Arg, P = 5.38 × 10-10, odds ratio (OR) = 0.68…

0301 basic medicineLinkage disequilibrium[SDV]Life Sciences [q-bio]MedizinSequence HomologyGenome-wide association studygenetics [Alzheimer Disease]metabolism [Microglia]Linkage Disequilibrium0302 clinical medicinegenetics [Protein Interaction Maps]genetics [Membrane Glycoproteins]Gene FrequencyImmunologicgenetics [Adaptor Proteins Signal Transducing]Receptorsgenetics [Exome]Odds RatioInnategenetics [Receptors Immunologic]ExomeProtein Interaction Mapsgenetics [Genetic Predisposition to Disease]Receptors ImmunologicABI3 protein humanGeneticsAdaptor Proteins Signal Transducing; Alzheimer Disease; Amino Acid Sequence; Case-Control Studies; Exome; Gene Expression Profiling; Gene Frequency; Genetic Predisposition to Disease; Genotype; Humans; Immunity Innate; Linkage Disequilibrium; Membrane Glycoproteins; Microglia; Odds Ratio; Phospholipase C gamma; Protein Interaction Maps; Receptors Immunologic; Sequence Homology Amino Acid; Polymorphism Single Nucleotide; GeneticsMembrane GlycoproteinsAdaptor ProteinsSingle NucleotideAdaptor Proteins Signal Transducing; Alzheimer Disease; Amino Acid Sequence; Case-Control Studies; Exome; Gene Expression Profiling; Gene Frequency; Genetic Predisposition to Disease; Genotype; Humans; Immunity Innate; Linkage Disequilibrium; Membrane Glycoproteins; Microglia; Odds Ratio; Phospholipase C gamma; Protein Interaction Maps; Receptors Immunologic; Sequence Homology Amino Acid; Polymorphism Single Nucleotide3. Good health[SDV] Life Sciences [q-bio]Amino AcidSettore MED/26 - NEUROLOGIAgenetics [Phospholipase C gamma][SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]MicrogliaAlzheimer's diseaseCommon disease-common variantGenotypeBiologyPolymorphism Single NucleotideArticle03 medical and health sciencesAlzheimer Diseaseddc:570medicineJournal ArticleGeneticsHumansGenetic Predisposition to Disease[SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]Amino Acid SequencePolymorphismAllele frequencyAdaptor Proteins Signal TransducingTREM2 protein humanSequence Homology Amino AcidTREM2Phospholipase C gammaGene Expression ProfilingCase-control studySignal TransducingImmunitymedicine.diseaseR1Immunity InnateMinor allele frequencygenetics [Immunity Innate]030104 developmental biologyCase-Control StudiesHuman medicine030217 neurology & neurosurgery
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Additional file 6 of Genome-wide association studies identify 137 genetic loci for DNA methylation biomarkers of aging

2021

Additional file 6. Review history.

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Genome-wide association studies identify 137 loci for DNA methylation biomarkers of ageing

2020

AbstractBiological ageing estimators derived from DNA methylation (DNAm) data are heritable and correlate with morbidity and mortality. Leveraging DNAm and SNP data from &gt;41,000 individuals, we identify 137 genome-wide significant loci (113 novel) from meta-analyses of four epigenetic clocks and epigenetic surrogate markers for granulocyte proportions and plasminogen activator inhibitor 1 levels, respectively. We report strong genetic correlations with longevity and lifestyle factors such as smoking, education, and obesity. Significant associations are observed in polygenic risk score analysis and to a lesser extent in Mendelian randomization analyses. This study illuminates the genetic …

African americanGenetics0303 health sciencesdNaMGenome-wide association studyBiologyGenome3. Good health03 medical and health sciences0302 clinical medicineAgeingDNA methylationParental longevityEpigenetics030217 neurology & neurosurgery030304 developmental biology
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Large-Scale Candidate Gene Analysis in Whites and African Americans Identifies IL6R Polymorphism in Relation to Atrial Fibrillation The National Hear…

2011

Background— The genetic background of atrial fibrillation (AF) in whites and African Americans is largely unknown. Genes in cardiovascular pathways have not been systematically investigated. Methods and Results— We examined a panel of approximately 50 000 common single-nucleotide polymorphisms (SNPs) in 2095 cardiovascular candidate genes and AF in 3 cohorts with participants of European (n=18 524; 2260 cases) or African American descent (n=3662; 263 cases) in the National Heart, Lung, and Blood Institute's Candidate Gene Association Resource. Results in whites were followed up in the German Competence Network for AF (n=906, 468 cases). The top result was assessed in relation to incident i…

medicine.medical_specialtyCandidate geneINTERLEUKIN-6ATHEROSCLEROSIS RISKSingle-nucleotide polymorphismVARIANTSDISEASEINFLAMMATIONDESIGNsingle nucleotide polymorphismInternal medicinecohort studyGeneticsmedicineatrial fibrillationCHROMOSOME 4Q25Genetics (clinical)Geneticsbusiness.industryHazard ratioAtrial fibrillationrace/ethnicitymedicine.diseaseC-REACTIVE PROTEINEUROPEAN ANCESTRYISCHEMIC-STROKERelative riskCohortepidemiologyCardiology and Cardiovascular MedicinebusinessCandidate Gene AnalysisCohort study
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Additional file 2 of Genome-wide association studies identify 137 genetic loci for DNA methylation biomarkers of aging

2021

Additional file 2. Supplementary Tables -Tables S1-S31.

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Additional file 2 of Genome-wide association studies identify 137 genetic loci for DNA methylation biomarkers of aging

2021

Additional file 2. Supplementary Tables -Tables S1-S31.

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