title: Assessing the role of the TREM2 p.R47H variant as a risk factor for Alzheimer's disease and frontotemporal dementia.
abstract: A non-synonymous genetic rare variant, rs75932628-T (p.R47H), in the TREM2 gene has recently been reported to be a strong genetic risk factor for Alzheimer's disease (AD). Also, rare recessive mutations have been associated with frontotemporal dementia (FTD). We aimed to investigate the role of p.R47H variant in AD and FTD through a multi-center study comprising 3172 AD and 682 FTD patients and 2169 healthy controls from Spain. We found that 0.6% of AD patients carried this variant compared to 0.1% of controls (odds ratio [OR] = 4.12, 95% confidence interval [CI] = 1.21-14.00, p = 0.014). A meta-analysis comprising 32,598 subjects from 4 previous studies demonstrated the large effect of the p.R47H variant in AD risk (OR = 4.11, 95% CI = 2.99-5.68, p = 5.27×10(-18)). We did not find an association between p.R47H and age of onset of AD or family history of dementia. Finally, none of the FTD patients harbored this genetic variant. These data strongly support the important role of p.R47H in AD risk, and suggest that this rare genetic variant is not related to FTD.
authors.affiliation: Alzheimer Research Center and Memory Clinic, Fundació ACE, Institut Català de Neurociències Aplicades, Barcelona, Spain.
authors.forename: Agustín
authors.initials: A
authors.lastname: Ruiz
authors.forename: Oriol
authors.initials: O
authors.lastname: Dols-Icardo
authors.forename: María J
authors.initials: MJ
authors.lastname: Bullido
authors.forename: Pau
authors.initials: P
authors.lastname: Pastor
authors.forename: Eloy
authors.initials: E
authors.lastname: Rodríguez-Rodríguez
authors.forename: Adolfo
authors.initials: A
authors.lastname: López de Munain
authors.forename: Marian M
authors.initials: MM
authors.lastname: de Pancorbo
authors.forename: Jordi
authors.initials: J
authors.lastname: Pérez-Tur
authors.forename: Victoria
authors.initials: V
authors.lastname: Alvarez
authors.forename: Anna
authors.initials: A
authors.lastname: Antonell
authors.forename: Jesús
authors.initials: J
authors.lastname: López-Arrieta
authors.forename: Isabel
authors.initials: I
authors.lastname: Hernández
authors.forename: Lluís
authors.initials: L
authors.lastname: Tárraga
authors.forename: Mercè
authors.initials: M
authors.lastname: Boada
authors.forename: Alberto
authors.initials: A
authors.lastname: Lleó
authors.forename: Rafael
authors.initials: R
authors.lastname: Blesa
authors.forename: Ana
authors.initials: A
authors.lastname: Frank-García
authors.forename: Isabel
authors.initials: I
authors.lastname: Sastre
authors.forename: Cristina
authors.initials: C
authors.lastname: Razquin
authors.forename: Sara
authors.initials: S
authors.lastname: Ortega-Cubero
authors.forename: Elena
authors.initials: E
authors.lastname: Lorenzo
authors.forename: Pascual
authors.initials: P
authors.lastname: Sánchez-Juan
authors.forename: Onofre
authors.initials: O
authors.lastname: Combarros
authors.forename: Fermín
authors.initials: F
authors.lastname: Moreno
authors.forename: Ana
authors.initials: A
authors.lastname: Gorostidi
authors.forename: Xabier
authors.initials: X
authors.lastname: Elcoroaristizabal
authors.forename: Miquel
authors.initials: M
authors.lastname: Baquero
authors.forename: Eliecer
authors.initials: E
authors.lastname: Coto
authors.forename: Raquel
authors.initials: R
authors.lastname: Sánchez-Valle
authors.forename: Jordi
authors.initials: J
authors.lastname: Clarimón
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D000544:Alzheimer Disease / Q000235:genetics*; D015331:Cohort Studies; D005260:Female; D057180:Frontotemporal Dementia / Q000235:genetics*; D005808:Genes, Recessive / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000235:genetics; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics*; D015201:Meta-Analysis as Topic; D008875:Middle Aged; D015337:Multicenter Studies as Topic; D009154:Mutation; D011110:Polymorphism, Genetic / Q000235:genetics*; D011971:Receptors, Immunologic / Q000235:genetics*; D012307:Risk Factors; D013030:Spain
chemical_list: D008562:Membrane Glycoproteins; D011971:Receptors, Immunologic; C498715:TREM2 protein, human
keywords: Alzheimer's disease; Frontotemporal dementia; Genetic association; Rare variant; TREM2; p.R47H