title: The MAPT H1c risk haplotype is associated with increased expression of tau and especially of 4 repeat containing transcripts.
abstract: Previously we have shown that the H1c haplotype on the background of the H1 clade of haplotypes at the MAPT locus is associated with increased risk for progressive supranuclear palsy (PSP), corticobasal degeneration (CBD) and Alzheimer's disease (AD). Here we replicated the association with AD in an additional autopsy confirmed series. We show that this haplotype increases both the expression of total MAPT transcript as well as specifically increasing the proportion of 4 microtubule binding repeat containing transcripts. We discuss these findings both in terms of the problems facing the dissection of the etiologies of complex traits and the pathogenesis of the tauopathies.
authors.affiliation: Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, 35 Convent Drive, Bethesda, MD 20892-3707, USA.
authors.forename: Amanda J
authors.initials: AJ
authors.lastname: Myers
authors.forename: Alan M
authors.initials: AM
authors.lastname: Pittman
authors.forename: Alice S
authors.initials: AS
authors.lastname: Zhao
authors.forename: Kristen
authors.initials: K
authors.lastname: Rohrer
authors.forename: Mona
authors.initials: M
authors.lastname: Kaleem
authors.forename: Lauren
authors.initials: L
authors.lastname: Marlowe
authors.forename: Andrew
authors.initials: A
authors.lastname: Lees
authors.forename: Doris
authors.initials: D
authors.lastname: Leung
authors.forename: Ian G
authors.initials: IG
authors.lastname: McKeith
authors.forename: Robert H
authors.initials: RH
authors.lastname: Perry
authors.forename: Chris M
authors.initials: CM
authors.lastname: Morris
authors.forename: John Q
authors.initials: JQ
authors.lastname: Trojanowski
authors.forename: Christopher
authors.initials: C
authors.lastname: Clark
authors.forename: Jason
authors.initials: J
authors.lastname: Karlawish
authors.forename: Steve
authors.initials: S
authors.lastname: Arnold
authors.forename: Mark S
authors.initials: MS
authors.lastname: Forman
authors.forename: Vivianna
authors.initials: V
authors.lastname: Van Deerlin
authors.forename: Rohan
authors.initials: R
authors.lastname: de Silva
authors.forename: John
authors.initials: J
authors.lastname: Hardy
mesh_terms: D017668:Age of Onset; D000483:Alleles; D000544:Alzheimer Disease / Q000453:epidemiology / Q000235:genetics*; D045744:Cell Line, Tumor; D005786:Gene Expression Regulation; D020022:Genetic Predisposition to Disease / Q000453:epidemiology; D006239:Haplotypes; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D009447:Neuroblastoma; D012333:RNA, Messenger / Q000235:genetics; D012091:Repetitive Sequences, Nucleic Acid; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012307:Risk Factors; D024801:Tauopathies / Q000453:epidemiology / Q000235:genetics*; D016875:tau Proteins / Q000235:genetics*
chemical_list: C054369:MAPT protein, human; D012333:RNA, Messenger; D016875:tau Proteins