title: Increased DNA methylation near TREM2 is consistently seen in the superior temporal gyrus in Alzheimer's disease brain.
abstract: Although mutations within the TREM2 gene have been robustly associated with Alzheimer's disease, it is not known whether alterations in the regulation of this gene are also involved in pathogenesis. Here, we present data demonstrating increased DNA methylation in the superior temporal gyrus in Alzheimer's disease brain at a CpG site located 289 bp upstream of the transcription start site of the TREM2 gene in 3 independent study cohorts using 2 different technologies (Illumina Infinium 450K methylation beadchip and pyrosequencing). A meta-analysis across all 3 cohorts reveals consistent AD-associated hypermethylation (p = 3.47E-08). This study highlights that extending genetic studies of TREM2 in AD to investigate epigenetic changes may nominate additional mechanisms by which disruption to this gene increases risk.
authors: Institute of Biomedical and Clinical Science, University of Exeter Medical School, RILD, University of Exeter, Devon, UK.
authors: Adam R
authors: AR
authors: Smith
authors: Institute of Biomedical and Clinical Science, University of Exeter Medical School, RILD, University of Exeter, Devon, UK.
authors: Rebecca G
authors: RG
authors: Smith
authors: School of Biological and Chemical Sciences, Queen Mary University of London, London, UK.
authors: Daniel
authors: D
authors: Condliffe
authors: Institute of Biomedical and Clinical Science, University of Exeter Medical School, RILD, University of Exeter, Devon, UK.
authors: Eilis
authors: E
authors: Hannon
authors: School of Biological Sciences, University of Essex, Wivenhoe Park, Colchester, UK.
authors: Leonard
authors: L
authors: Schalkwyk
authors: Institute of Biomedical and Clinical Science, University of Exeter Medical School, RILD, University of Exeter, Devon, UK; Social, Genetic and Developmental Psychiatry (SGDP) Centre, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.
authors: Jonathan
authors: J
authors: Mill
authors: Institute of Biomedical and Clinical Science, University of Exeter Medical School, RILD, University of Exeter, Devon, UK. Electronic address: k.lunnon@exeter.ac.uk.
authors: Katie
authors: K
authors: Lunnon
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000235:genetics* / Q000378:metabolism*; D015331:Cohort Studies; D018899:CpG Islands / Q000235:genetics; D019175:DNA Methylation; D044127:Epigenesis, Genetic / Q000235:genetics; D005260:Female; D056726:Genetic Association Studies; D006801:Humans; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics*; D015201:Meta-Analysis as Topic; D008875:Middle Aged; D011971:Receptors, Immunologic / Q000235:genetics*; D013702:Temporal Lobe / Q000378:metabolism*
chemical_list: D008562:Membrane Glycoproteins; D011971:Receptors, Immunologic; C498715:TREM2 protein, human
keywords: AD; Alzheimer's disease; Braak stage; Brain; DNA methylation; Epigenetics; TREM2