title: More evidence for association of a rare TREM2 mutation (R47H) with Alzheimer's disease risk.
abstract: Over 20 risk loci have been identified for late-onset Alzheimer's disease (LOAD), most of which display relatively small effect sizes. Recently, a rare missense (R47H) variant, rs75932628 in TREM2, has been shown to mediate LOAD risk substantially in Icelandic and Caucasian populations. Here, we present more evidence for the association of the R47H with LOAD risk in a Caucasian population comprising 4567 LOAD cases and controls. Our results show that carriers of the R47H variant have a significantly increased risk for LOAD (odds ratio = 7.40, p = 3.66E-06). In addition to Alzheimer's disease risk, we also examined the association of R47H with Alzheimer's disease-related phenotypes, including age-at-onset, psychosis, and amyloid deposition but found no significant association. Our results corroborate those of other studies implicating TREM2 as an LOAD risk locus and indicate the need to determine its biological role in the context of neurodegeneration.
authors.affiliation: Department of Human Genetics, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA, USA.
authors.forename: Samantha L
authors.initials: SL
authors.lastname: Rosenthal
authors.affiliation: Department of Human Genetics, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA, USA.
authors.forename: Mikhil N
authors.initials: MN
authors.lastname: Bamne
authors.affiliation: Department of Human Genetics, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA, USA.
authors.forename: Xingbin
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Neurology, School of Medicine, University of Pittsburgh, Pittsburgh, PA, USA.
authors.forename: Sarah
authors.initials: S
authors.lastname: Berman
authors.affiliation: Department of Neurology, School of Medicine, University of Pittsburgh, Pittsburgh, PA, USA.
authors.forename: Beth E
authors.initials: BE
authors.lastname: Snitz
authors.affiliation: Department of Psychiatry, School of Medicine, University of Pittsburgh, Pittsburgh, PA, USA.
authors.forename: William E
authors.initials: WE
authors.lastname: Klunk
authors.affiliation: Department of Neurology, School of Medicine, University of Pittsburgh, Pittsburgh, PA, USA; Department of Psychiatry, School of Medicine, University of Pittsburgh, Pittsburgh, PA, USA; VISN 4 Mental Illness Research, Education and Clinical Center (MIRECC), VA Pittsburgh Healthcare System, Pittsburgh, PA, USA.
authors.forename: Robert A
authors.initials: RA
authors.lastname: Sweet
authors.affiliation: Department of Human Genetics, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA, USA.
authors.forename: F Yesim
authors.initials: FY
authors.lastname: Demirci
authors.affiliation: Department of Neurology, School of Medicine, University of Pittsburgh, Pittsburgh, PA, USA.
authors.forename: Oscar L
authors.initials: OL
authors.lastname: Lopez
authors.affiliation: Department of Human Genetics, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA, USA. Electronic address: kamboh@pitt.edu.
authors.forename: M Ilyas
authors.initials: MI
authors.lastname: Kamboh
mesh_terms: D017668:Age of Onset; D000368:Aged; D000544:Alzheimer Disease / Q000453:epidemiology / Q000235:genetics* / Q000378:metabolism; D016229:Amyloid beta-Peptides / Q000378:metabolism; D001921:Brain / Q000378:metabolism; D005260:Female; D056726:Genetic Association Studies; D006579:Heterozygote; D006801:Humans; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics*; D020125:Mutation, Missense; D010641:Phenotype; D011971:Receptors, Immunologic / Q000235:genetics*; D012306:Risk; D044465:White People
chemical_list: D016229:Amyloid beta-Peptides; D008562:Membrane Glycoproteins; D011971:Receptors, Immunologic; C498715:TREM2 protein, human
keywords: LOAD; Rare variants; TREM2