0000000000237175

AUTHOR

Brendan J. Keating

showing 5 related works from this author

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 analysis in dilated cardiomyopathy reveals two new key players in systolic heart failure on chromosome 3p25.1 and 22q11.23

2020

SummaryWe present the results of the largest genome wide association study (GWAS) performed so far in dilated cardiomyopathy (DCM), a leading cause of systolic heart failure and cardiovascular death, with 2,719 cases and 4,440 controls in the discovery population. We identified and replicated two new DCM-associated loci, one on chromosome 3p25.1 (lead SNP rs62232870, p = 8.7 × 10−11 and 7.7 × 10−4 in the discovery and replication step, respectively) and the second on chromosome 22q11.23 (lead SNP rs7284877, p = 3.3 × 10−8 and 1.4 × 10−3 in the discovery and replication step, respectively) while confirming two previously identified DCM loci on chromosome 10 and 1, BAG3 and HSPB7. The genetic…

Genetics0303 health scienceseducation.field_of_studyPopulationGenome-wide association studyDilated cardiomyopathyLocus (genetics)030204 cardiovascular system & hematologyBiologymedicine.diseaseGenomeGenetic architecture03 medical and health sciences0302 clinical medicinemedicineSNPeducationGene030304 developmental biology
researchProduct

Genome-wide Trans-ethnic Meta-analysis Identifies Seven Genetic Loci Influencing Erythrocyte Traits and a Role for RBPMS in Erythropoiesis

2017

Genome-wide association studies (GWASs) have identified loci for erythrocyte traits in primarily European ancestry populations. We conducted GWAS meta-analyses of six erythrocyte traits in 71,638 individuals from European, East Asian, and African ancestries using a Bayesian approach to account for heterogeneity in allelic effects and variation in the structure of linkage disequilibrium between ethnicities. We identified seven loci for erythrocyte traits including a locus (RBPMS/GTF2E2) associated with mean corpuscular hemoglobin and mean corpuscular volume. Statistical fine-mapping at this locus pointed to RBPMS at this locus and excluded nearby GTF2E2. Using zebrafish morpholino to evaluat…

0301 basic medicineMaleLinkage disequilibriumAsiaErythrocytesGenome-wide association studyLocus (genetics)RBPMS030105 genetics & heredityBiologyEasternGenomeMedical and Health SciencesArticleLinkage Disequilibrium03 medical and health sciencesGeneticsEthnicityAnimalsHumansErythropoiesisAlleleGenetics (clinical)Loss functionAllelesZebrafishGenetic associationGeneticsGenetics & HeredityAsia EasternHuman GenomeRacial GroupsRNA-Binding ProteinsBioBank Japan ProjectBayes TheoremHematologyBiological SciencesR13. Good healthEurope030104 developmental biologyAfricaFemaleGenome-Wide Association Study
researchProduct

Genome-wide association analysis in dilated cardiomyopathy reveals two new players in systolic heart failure on chromosomes 3p25.1 and 22q11.23

2021

Abstract Aims  Our objective was to better understand the genetic bases of dilated cardiomyopathy (DCM), a leading cause of systolic heart failure. Methods and results  We conducted the largest genome-wide association study performed so far in DCM, with 2719 cases and 4440 controls in the discovery population. We identified and replicated two new DCM-associated loci on chromosome 3p25.1 [lead single-nucleotide polymorphism (SNP) rs62232870, P = 8.7 × 10−11 and 7.7 × 10−4 in the discovery and replication steps, respectively] and chromosome 22q11.23 (lead SNP rs7284877, P = 3.3 × 10−8 and 1.4 × 10−3 in the discovery and replication steps, respectively), while confirming two previously identif…

Cardiac & Cardiovascular SystemsCardiomyopathy Dilated/genetics[SDV]Life Sciences [q-bio]Signal Transducing/geneticsDilated cardiomyopathyGenome-wide association studyAdaptor Proteins Signal Transducing/genetics030204 cardiovascular system & hematologyTAURINE0302 clinical medicineGWASMedicinePOSITION STATEMENT1102 Cardiorespiratory Medicine and HaematologyGenetics0303 health scienceseducation.field_of_studyGenetic Predisposition to Disease/geneticsAdaptor ProteinsDilated cardiomyopathy4C-sequencingPolymorphism Single Nucleotide/geneticsGenetic risk scoreCardiology and Cardiovascular MedicineLife Sciences & BiomedicineSingle Nucleotide/geneticsCardiomyopathy DilatedCardiomyopathyPopulationLocus (genetics)Single-nucleotide polymorphismPolymorphism Single NucleotideChromosomes03 medical and health sciencesSystolic/geneticsHeart Failure Systolic/geneticsSNPAnimalsHumansGenetic Predisposition to DiseaseAllelePolymorphismeducationImputationAdaptor Proteins Signal Transducing030304 developmental biologyHeart FailureScience & Technologybusiness.industryWORKING GROUP1103 Clinical Sciencesmedicine.diseaseGenetic architectureCardiovascular System & Hematology Dilated cardiomyopathyDilated/geneticsCardiovascular System & Cardiology[SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologiebusinessApoptosis Regulatory ProteinsHeart Failure SystolicGenome-Wide Association Study
researchProduct

Genome-wide and gene-centric analyses of circulating myeloperoxidase levels in the charge and care consortia

2013

Increased systemic levels of myeloperoxidase (MPO) are associated with the risk of coronary artery disease (CAD). To identify the genetic factors that are associated with circulating MPO levels, we carried out a genome-wide association study (GWAS) and a gene-centric analysis in subjects of European ancestry and African Americans (AAs). A locus on chromosome 1q31.1 containing the complement factor H (CFH) gene was strongly associated with serum MPO levels in 9305 subjects of European ancestry (lead SNP rs800292; P = 4.89 × 10(-41)) and in 1690 AA subjects (rs505102; P = 1.05 × 10(-8)). Gene-centric analyses in 8335 subjects of European ancestry additionally identified two rare M…

AdultMaleGenotypeLocus (genetics)Single-nucleotide polymorphismGenome-wide association studyCoronary Artery Disease030204 cardiovascular system & hematologyBiologyPolymorphism Single NucleotideGene Expression Regulation EnzymologicWhite PeopleYoung Adult03 medical and health sciences0302 clinical medicineGenotypeGeneticsHumansSNPMolecular BiologyGenetic Association StudiesGenetics (clinical)AgedPeroxidase030304 developmental biology0303 health sciencesAssociation Studies ArticlesCase-control studyGenetic VariationGeneral MedicineMiddle Aged3. Good healthBlack or African AmericanCase-Control StudiesComplement Factor HFactor HMyeloperoxidaseImmunologybiology.proteinFemaleGenome-Wide Association StudyHuman Molecular Genetics
researchProduct