| Literature DB >> 25936935 |
Christina M Lill1, Aina Rengmark2, Lasse Pihlstrøm2, Isabella Fogh3, Aleksey Shatunov3, Patrick M Sleiman4, Li-San Wang5, Tian Liu6, Christina F Lassen7, Esther Meissner8, Panos Alexopoulos9, Andrea Calvo10, Adriano Chio11, Nil Dizdar12, Frank Faltraco13, Lars Forsgren14, Julia Kirchheiner15, Alexander Kurz9, Jan P Larsen16, Maria Liebsch8, Jan Linder14, Karen E Morrison17, Hans Nissbrandt18, Markus Otto15, Jens Pahnke19, Amanda Partch5, Gabriella Restagno20, Dan Rujescu21, Cathrin Schnack15, Christopher E Shaw3, Pamela J Shaw22, Hayrettin Tumani15, Ole-Bjørn Tysnes23, Otto Valladares5, Vincenzo Silani24, Leonard H van den Berg25, Wouter van Rheenen25, Jan H Veldink25, Ulman Lindenberger6, Elisabeth Steinhagen-Thiessen26, Stefan Teipel27, Robert Perneczky28, Hakon Hakonarson4, Harald Hampel29, Christine A F von Arnim15, Jørgen H Olsen7, Vivianna M Van Deerlin5, Ammar Al-Chalabi3, Mathias Toft2, Beate Ritz30, Lars Bertram31.
Abstract
A rare variant in TREM2 (p.R47H, rs75932628) was recently reported to increase the risk of Alzheimer's disease (AD) and, subsequently, other neurodegenerative diseases, i.e. frontotemporal lobar degeneration (FTLD), amyotrophic lateral sclerosis (ALS), and Parkinson's disease (PD). Here we comprehensively assessed TREM2 rs75932628 for association with these diseases in a total of 19,940 previously untyped subjects of European descent. These data were combined with those from 28 published data sets by meta-analysis. Furthermore, we tested whether rs75932628 shows association with amyloid beta (Aβ42) and total-tau protein levels in the cerebrospinal fluid (CSF) of 828 individuals with AD or mild cognitive impairment. Our data show that rs75932628 is highly significantly associated with the risk of AD across 24,086 AD cases and 148,993 controls of European descent (odds ratio or OR = 2.71, P = 4.67 × 10(-25)). No consistent evidence for association was found between this marker and the risk of FTLD (OR = 2.24, P = .0113 across 2673 cases/9283 controls), PD (OR = 1.36, P = .0767 across 8311 cases/79,938 controls) and ALS (OR = 1.41, P = .198 across 5544 cases/7072 controls). Furthermore, carriers of the rs75932628 risk allele showed significantly increased levels of CSF-total-tau (P = .0110) but not Aβ42 suggesting that TREM2's role in AD may involve tau dysfunction.Entities:
Keywords: Alzheimer disease; Amyotrophic lateral sclerosis; Frontotemporal lobar degeneration; GWAS; Genetic association; Imputation; Meta-analysis; Neurodegenerative disease; Parkinson disease; R47H; Rare variant; TREM2; rs75932628
Mesh：
Substances：
Year: 2015 PMID： 25936935 PMCID： PMC4627856 DOI： 10.1016/j.jalz.2014.12.009
Source DB: PubMed Journal: Alzheimers Dement ISSN： 1552-5260 Impact factor: 21.566