title: Alzheimer disease (AD) specific transcription, DNA methylation and splicing in twenty AD associated loci.
abstract: Genome-wide association studies have identified twenty loci associated with late-onset Alzheimer disease (LOAD). We examined each of the twenty loci, specifically the ±50kb region surrounding the most strongly associated variant, for changes in gene(s) transcription specific to LOAD. Post-mortem human brain samples were examined for expression, methylation, and splicing differences. LOAD specific differences were detected by comparing LOAD to normal and "disease" controls. Eight loci, prominently ABCA7, contain LOAD specific differences. Significant changes in the CELF1 and ZCWPW1 loci occurred in genes not located nearest the associated variant, suggesting that these genes should be investigated further as LOAD candidates.
authors.affiliation: John P. Hussman Institute for Human Genomics, University of Miami, Miller School of Medicine, Miami, FL 33136, USA; Dr. John T. Macdonald Foundation Department of Human Genetics, University of Miami, Miller School of Medicine, Miami, FL 33136, USA.
authors.forename: Crystal
authors.initials: C
authors.lastname: Humphries
authors.affiliation: John P. Hussman Institute for Human Genomics, University of Miami, Miller School of Medicine, Miami, FL 33136, USA.
authors.forename: Martin A
authors.initials: MA
authors.lastname: Kohli
authors.affiliation: John P. Hussman Institute for Human Genomics, University of Miami, Miller School of Medicine, Miami, FL 33136, USA.
authors.forename: Patrice
authors.initials: P
authors.lastname: Whitehead
authors.affiliation: Department of Neurology, University of Miami, Miller School of Medicine, FL 33136, USA.
authors.forename: Deborah C
authors.initials: DC
authors.lastname: Mash
authors.affiliation: John P. Hussman Institute for Human Genomics, University of Miami, Miller School of Medicine, Miami, FL 33136, USA; Dr. John T. Macdonald Foundation Department of Human Genetics, University of Miami, Miller School of Medicine, Miami, FL 33136, USA.
authors.forename: Margaret A
authors.initials: MA
authors.lastname: Pericak-Vance
authors.affiliation: John P. Hussman Institute for Human Genomics, University of Miami, Miller School of Medicine, Miami, FL 33136, USA; Dr. John T. Macdonald Foundation Department of Human Genetics, University of Miami, Miller School of Medicine, Miami, FL 33136, USA. Electronic address: jgilbert@med.miami.edu.
authors.forename: John
authors.initials: J
authors.lastname: Gilbert
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000235:genetics* / Q000378:metabolism; D016022:Case-Control Studies; D019175:DNA Methylation; D056426:Genetic Loci; D006801:Humans; D008297:Male; D012326:RNA Splicing; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism*
chemical_list: D012333:RNA, Messenger
keywords: DNA methylation; Dementia with Lewy bodies; Differential expression; Genome-wide association study; Late-onset Alzheimer disease; Microarray; RNA-Seq; Splicing; Transcription