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Series GSE59685 Query DataSets for GSE59685
Status Public on Aug 17, 2014
Title Cross-tissue methylomic profiling implicates cortical deregulation of ANK1 in Alzheimer’s disease neuropathology
Organism Homo sapiens
Experiment type Methylation profiling by array
Summary Alzheimer’s disease (AD) is a chronic neurodegenerative disorder that is characterized by progressive neuropathology and cognitive decline. We performed a cross-tissue analysis of methylomic variation in AD using samples from three independent human post-mortem brain cohorts. We identified a differentially methylated region in the ankyrin 1 (ANK1) gene that was associated with neuropathology in the entorhinal cortex, a primary site of AD manifestation. This region was confirmed as being substantially hypermethylated in two other cortical regions (superior temporal gyrus and prefrontal cortex), but not in the cerebellum, a region largely protected from neurodegeneration in AD, or whole blood obtained pre-mortem from the same individuals. Neuropathology-associated ANK1 hypermethylation was subsequently confirmed in cortical samples from three independent brain cohorts. This study represents, to the best of our knowledge, the first epigenome-wide association study of AD employing a sequential replication design across multiple tissues and highlights the power of this approach for identifying methylomic variation associated with complex disease.
Overall design For the first (discovery) stage of our analysis, we used multiple tissues from donors (N = 122) archived in the MRC London Brainbank for Neurodegenerative Disease. From each donor, we isolated genomic DNA from four brain regions (EC, superior temporal gyrus (STG), prefrontal cortex (PFC) and CER) and, where available, from whole blood obtained pre-mortem. Our analyses focused on identifying differentially methylated positions (DMPs) associated with Braak staging, a standardized measure of neurofibrillary tangle burden determined at autopsy.
Contributor(s) Lunnon K, Smith R, Hannon E, De Jager PL, Srivastava G, Volta M, Troakes C, Al-Sarraj S, Burrage J, Macdonald R, Condliffe D, Harries LW, Katsel P, Haroutunian V, Kaminsky Z, Joachim C, Powell J, Lovestone S, Bennett DA, Schalkwyk LC, Mill J
Citation(s) 25129077, 26457534
Submission date Jul 23, 2014
Last update date Oct 07, 2019
Contact name Leonard C Schalkwyk
Organization name King's College London
Department IOP-SGDP
Street address De Crespigny Park
City London
ZIP/Postal code SE5 8AF
Country United Kingdom
Platforms (1)
GPL13534 Illumina HumanMethylation450 BeadChip (HumanMethylation450_15017482)
Samples (531)
GSM1443249 entorhinal cortex_subject_1
GSM1443250 whole blood_subject_1
GSM1443251 frontal cortex_subject_1
BioProject PRJNA256002

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE59685_RAW.tar 183.1 Mb (http)(custom) TAR
GSE59685_SampleBarcode_Re-analyzedGSMs_NewGSMs.txt.gz 3.8 Kb (ftp)(http) TXT
GSE59685_betas.csv.gz 1.9 Gb (ftp)(http) CSV
GSE59685_signal_intensities.csv.gz 1.5 Gb (ftp)(http) CSV
Processed data are available on Series record

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