0000000000920080

AUTHOR

Vilmantas Giedraitis

showing 2 related works from this author

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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Genome Analyses of >200,000 Individuals Identify 58 Loci for Chronic Inflammation and Highlight Pathways that Link Inflammation and Complex Disorders

2018

International audience; C-reactive protein (CRP) is a sensitive biomarker of chronic low-grade inflammation and is associated with multiple complex diseases. The genetic determinants of chronic inflammation remain largely unknown, and the causal role of CRP in several clinical outcomes is debated. We performed two genome-wide association studies (GWASs), on HapMap and 1000 Genomes imputed data, of circulating amounts of CRP by using data from 88 studies comprising 204,402 European individuals. Additionally, we performed in silico functional analyses and Mendelian randomization analyses with several clinical outcomes. The GWAS meta-analyses of CRP revealed 58 distinct genetic loci (p < 5 × 1…

0301 basic medicineMaleNetherlands Twin Register (NTR)Bipolar DisorderLD SCORE REGRESSION[SDV]Life Sciences [q-bio]Genome-wide association study[SDV.GEN] Life Sciences [q-bio]/GeneticsBody Mass Indexinflammatory disorder80 and overWIDE ASSOCIATIONEPIDEMIOLOGYta318International HapMap ProjectChildGenetics (clinical)2. Zero hungerGeneticsGenetics & HeredityAged 80 and over[SDV.MHEP] Life Sciences [q-bio]/Human health and pathologyC-reactive proteingenome-wide association studyinflammationMendelian randomizationinflammatory disordersDEPICTcoronary artery diseaseschizophreniasystem biologysystem biologyDEPICTMendelian Randomization Analysis11 Medical And Health SciencesMiddle AgedC-reactive protein; coronary artery disease; DEPICT; genome-wide association study; inflammation; inflammatory disorders; Mendelian randomization; schizophrenia; system biology; Adolescent; Adult; Aged; Aged 80 and over; Biomarkers; Bipolar Disorder; Body Mass Index; C-Reactive Protein; Child; Female; Genetic Loci; Genome-Wide Association Study; Humans; Inflammation; Liver; Male; Mendelian Randomization Analysis; Metabolic Networks and Pathways; Middle Aged; Schizophrenia; Young Adult3. Good health[SDV] Life Sciences [q-bio]LiverMedical geneticsBiomarker (medicine)/dk/atira/pure/sustainabledevelopmentgoals/good_health_and_well_beingFemaleinflammatory disordersLife Sciences & BiomedicineMetabolic Networks and Pathwayscoronary artery diseaseHumanAdultmedicine.medical_specialtyAdolescentCHARGE Inflammation Working GroupC-reactive protein ; DEPICT ; Mendelian randomization ; coronary artery disease ; genome-wide association study ; inflammation ; inflammatory disorders ; schizophrenia ; system biologyBiologyIMMUNITYta3111ArticleC-reactive protein03 medical and health sciencesYoung AdultSDG 3 - Good Health and Well-beingMendelian randomizationGeneticsmedicine/dk/atira/pure/keywords/cohort_studies/netherlands_twin_register_ntr_Mendelian randomizationHumansCORONARY-HEART-DISEASEMendelian Randomization Analysi1000 Genomes ProjectMETAANALYSISGenetic associationAged[SDV.GEN]Life Sciences [q-bio]/GeneticsScience & Technologygenome-wide association studyta1184Metabolic Networks and PathwayBiomarkerINSTRUMENTS06 Biological SciencesMendelian Randomization Analysisschizophrenia030104 developmental biologyGenetic LociinflammationC-reactive protein; DEPICT; Mendelian randomization; coronary artery disease; genome-wide association study; inflammation; inflammatory disorders; schizophrenia; system biology[SDV.MHEP]Life Sciences [q-bio]/Human health and pathologyBiomarkersLifeLines Cohort Study
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