title: Diurnal and seasonal molecular rhythms in human neocortex and their relation to Alzheimer's disease.
abstract: Circadian and seasonal rhythms are seen in many species, modulate several aspects of human physiology, including brain functions such as mood and cognition, and influence many neurological and psychiatric illnesses. However, there are few data regarding the genome-scale molecular correlates underlying these rhythms, especially in the human brain. Here, we report widespread, site-specific and interrelated diurnal and seasonal rhythms of gene expression in the human brain, and show their relationship with parallel rhythms of epigenetic modification including histone acetylation, and DNA methylation. We also identify transcription factor-binding sites that may drive these effects. Further, we demonstrate that Alzheimer's disease pathology disrupts these rhythms. These data suggest that interrelated diurnal and seasonal epigenetic and transcriptional rhythms may be an important feature of human brain biology, and perhaps human biology more broadly, and that changes in such rhythms may be consequences of, or contributors to, diseases such as Alzheimer's disease.
authors.affiliation: Division of Neurology, Department of Medicine, Sunnybrook Health Sciences Centre, University of Toronto, 2075 Bayview Avenue, Room M1-600, Toronto M4N1X2, Ontario, Canada.
authors.forename: Andrew S P
authors.initials: AS
authors.lastname: Lim
authors.affiliation: Program in Translational Neuropsychiatric Genomics, Department of Neurology, Brigham and Women's Hospital, Harvard Medical School, 77 Avenue Louis Pasteur, NRB 168c, Boston, Massachusetts 02115, USA.|Program in Medical and Population Genetics, Broad Institute, 415 Main Street, Cambridge, Massachusetts 02142, USA.
authors.forename: Hans-Ulrich
authors.initials: HU
authors.lastname: Klein
authors.affiliation: Rush Alzheimer's Disease Center and Department of Neurological Sciences, Rush University Medical Center, 600 South Paulina Street, Chicago, Illinois 60612, USA.
authors.forename: Lei
authors.initials: L
authors.lastname: Yu
authors.affiliation: Program in Translational Neuropsychiatric Genomics, Department of Neurology, Brigham and Women's Hospital, Harvard Medical School, 77 Avenue Louis Pasteur, NRB 168c, Boston, Massachusetts 02115, USA.|Program in Medical and Population Genetics, Broad Institute, 415 Main Street, Cambridge, Massachusetts 02142, USA.
authors.forename: Lori B
authors.initials: LB
authors.lastname: Chibnik
authors.affiliation: Division of Neurology, Department of Medicine, Sunnybrook Health Sciences Centre, University of Toronto, 2075 Bayview Avenue, Room M1-600, Toronto M4N1X2, Ontario, Canada.
authors.forename: Sanam
authors.initials: S
authors.lastname: Ali
authors.affiliation: Program in Translational Neuropsychiatric Genomics, Department of Neurology, Brigham and Women's Hospital, Harvard Medical School, 77 Avenue Louis Pasteur, NRB 168c, Boston, Massachusetts 02115, USA.|Program in Medical and Population Genetics, Broad Institute, 415 Main Street, Cambridge, Massachusetts 02142, USA.
authors.forename: Jishu
authors.identifier: 0000-0002-3679-6579
authors.initials: J
authors.lastname: Xu
authors.affiliation: Rush Alzheimer's Disease Center and Department of Neurological Sciences, Rush University Medical Center, 600 South Paulina Street, Chicago, Illinois 60612, USA.
authors.forename: David A
authors.initials: DA
authors.lastname: Bennett
authors.affiliation: Program in Translational Neuropsychiatric Genomics, Department of Neurology, Brigham and Women's Hospital, Harvard Medical School, 77 Avenue Louis Pasteur, NRB 168c, Boston, Massachusetts 02115, USA.|Program in Medical and Population Genetics, Broad Institute, 415 Main Street, Cambridge, Massachusetts 02142, USA.
authors.forename: Philip L
authors.initials: PL
authors.lastname: De Jager
mesh_terms: D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000235:genetics* / Q000503:physiopathology*; D001665:Binding Sites; D056926:CLOCK Proteins / Q000235:genetics / Q000378:metabolism; D002940:Circadian Rhythm / Q000235:genetics*; D019175:DNA Methylation / Q000235:genetics; D044127:Epigenesis, Genetic; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D008297:Male; D019579:Neocortex / Q000503:physiopathology*; D012621:Seasons; D017423:Sequence Analysis, RNA; D013997:Time Factors; D014157:Transcription Factors / Q000378:metabolism; D059467:Transcriptome / Q000235:genetics
chemical_list: D014157:Transcription Factors; D056926:CLOCK Proteins