0000000000919911

AUTHOR

Ronald L. Hamilton

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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July 2003: 62-year-old female with progressive muscular weakness

2004

The July 2003 Case of the Month (COM). A 62-year-old female patient experienced progressive muscular weakness over the last ten years, involving shoulder and pelvic girdle muscles, paraspinal and facial muscles. A biopsy was taken from the left deltoid muscle where hepatitis vaccination had taken place 4 weeks previously. The specimen revealed macrophagic myofasciitis due to the injection of aluminium-bound vaccines. The finding can be reproduced experimentally by injecting vaccines in rats. The pathomechanism is supposed to involve immune stimulation due to long term persistence of the adjuvant. Macrophagic myofasciitis has been suggested to occasionally cause myopathy but is supposed to b…

Viral Hepatitis Vaccinesmedicine.medical_specialtyAluminum HydroxideMass SpectrometryCases of the Month: July to September 2003Pathology and Forensic MedicineDiagnosis DifferentialBiopsymedicineHumansMuscle SkeletalMyopathyInclusion BodiesHepatitisMuscle WeaknessPelvic girdlemedicine.diagnostic_testbusiness.industryMacrophagesGeneral NeuroscienceMacrophagic myofasciitisMiddle Agedmedicine.diseaseMuscular Dystrophy FacioscapulohumeralSurgeryVaccinationMicroscopy ElectronFacial musclesmedicine.anatomical_structureFemaleNeurology (clinical)medicine.symptombusinessProgressive muscular weaknessBrain Pathology
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