TY - JOUR
T1 - MAPT H1 haplotype is associated with late-onset Alzheimer's disease risk in APOE ε 4 noncarriers: Results from the dementia genetics Spanish consortium
AU - Pastor, Pau
AU - Moreno, Fermín
AU - Clarimón, Jordi
AU - Ruiz, Agustín
AU - Combarros, Onofre
AU - Calero, Miguel
AU - De Munain, Adolfo López
AU - Bullido, Maria J.
AU - De Pancorbo, Marian M.
AU - Carro, Eva
AU - Antonell, Anna
AU - Coto, Eliecer
AU - Ortega-Cubero, Sara
AU - Hernandez, Isabel
AU - Tárraga, Lluís
AU - Boada, Mercè
AU - Lleó, Alberto
AU - Dols-Icardo, Oriol
AU - Kulisevsky, Jaime
AU - Vázquez-Higuera, José Luis
AU - Infante, Jon
AU - Rábano, Alberto
AU - Fernández-Blázquez, Miguel Ángel
AU - Valentí, Meritxell
AU - Indakoetxea, Begoña
AU - Barandiarán, Myriam
AU - Gorostidi, Ana
AU - Frank-García, Ana
AU - Sastre, Isabel
AU - Lorenzo, Elena
AU - Pastor, María A.
AU - Elcoroaristizabal, Xabier
AU - Lennarz, Martina
AU - Maier, Wolfang
AU - Rámirez, Alfredo
AU - Serrano-Ríos, Manuel
AU - Lee, Suzee E.
AU - Sánchez-Juan, Pascual
PY - 2015/10/9
Y1 - 2015/10/9
N2 - © 2016 - IOS Press and the authors. The MAPT H1 haplotype has been linked to several disorders, but its relationship with Alzheimer's disease (AD) remains controversial. A rare variant in MAPT (p.A152T) has been linked with frontotemporal dementia (FTD) and AD. We genotyped H1/H2 and p.A152T MAPT in 11,572 subjects from Spain (4,327 AD, 563 FTD, 648 Parkinson's disease (PD), 84 progressive supranuclear palsy (PSP), and 5,950 healthy controls). Additionally, we included 101 individuals from 21 families with genetic FTD. MAPT p.A152T was borderline significantly associated with FTD [odds ratio (OR)=2.03; p=0.063], but not with AD. MAPT H1 haplotype was associated with AD risk (OR=1.12; p=0.0005). Stratification analysis showed that this association was mainly driven by APOE ε4 noncarriers (OR=1.14; p=0.0025). MAPT H1 was also associated with risk for PD (OR=1.30; p=0.0003) and PSP (OR=3.18; p=8.59 × 10-8) but not FTD. Our results suggest that the MAPT H1 haplotype increases the risk of PD, PSP, and non-APOE ε4 AD.
AB - © 2016 - IOS Press and the authors. The MAPT H1 haplotype has been linked to several disorders, but its relationship with Alzheimer's disease (AD) remains controversial. A rare variant in MAPT (p.A152T) has been linked with frontotemporal dementia (FTD) and AD. We genotyped H1/H2 and p.A152T MAPT in 11,572 subjects from Spain (4,327 AD, 563 FTD, 648 Parkinson's disease (PD), 84 progressive supranuclear palsy (PSP), and 5,950 healthy controls). Additionally, we included 101 individuals from 21 families with genetic FTD. MAPT p.A152T was borderline significantly associated with FTD [odds ratio (OR)=2.03; p=0.063], but not with AD. MAPT H1 haplotype was associated with AD risk (OR=1.12; p=0.0005). Stratification analysis showed that this association was mainly driven by APOE ε4 noncarriers (OR=1.14; p=0.0025). MAPT H1 was also associated with risk for PD (OR=1.30; p=0.0003) and PSP (OR=3.18; p=8.59 × 10-8) but not FTD. Our results suggest that the MAPT H1 haplotype increases the risk of PD, PSP, and non-APOE ε4 AD.
KW - A152T
KW - Alzheimer's disease
KW - frontotemporal dementia
KW - genetic association
KW - H1H2
KW - MAPT
U2 - 10.3233/JAD-150555
DO - 10.3233/JAD-150555
M3 - Article
SN - 1387-2877
VL - 49
SP - 343
EP - 352
JO - Journal of Alzheimer's Disease
JF - Journal of Alzheimer's Disease
IS - 2
ER -