期刊
NEUROBIOLOGY OF AGING
卷 35, 期 6, 页码 -出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.neurobiolaging.2013.12.010
关键词
TREM2; Genome-wide association studies; Conditional analysis; Endophenotype; Gene; Alzheimer's disease; Association
资金
- French National Foundation on Alzheimer's disease and related disorders
- LABEX (laboratory of excellence program investment for the future) DISTALZ grant (Development of Innovative Strategies for a Transdisciplinary approach to ALZheimer's disease)
- Caisse Nationale Maladie des Travailleurs Salaries
- Direction Generale de la Sante
- MGEN
- Institut de la Longevite
- Agence Francaise de Securite Sanitaire des Produits de Sante
- Aquitaine and Bourgogne Regional Councils
- Fondation de France
- French Ministry of Research and INSERM Cohortes et collections de donnees biologiques programme
- Alzheimers Research UK [ART-SB2010A-1, ARUK-TRFUS2012-1, ART-BIG2009-1, ARUK-PG2014-1, ARUK-TRFUS2012-3, ARUK-NCG2014A-1, ARUK-PG2014-2, ARUK-NCG2012B-1, ART-PhD2010-5, ARUK-PPG2013A-2] Funding Source: researchfish
- Medical Research Council [MR/L501517/1, MR/K013041/1, MC_G1000735, G0902227, MR/L010305/1] Funding Source: researchfish
- MRC [MC_G1000735, MR/K013041/1, G0902227] Funding Source: UKRI
TREM and TREM-like receptors are a structurally similar protein family encoded by genes clustered on chromosome 6p21.11. Recent studies have identified a rare coding variant (p. R47H) in TREM2 that confers a high risk for Alzheimer's disease (AD). In addition, common single nucleotide polymorphisms in this genomic region are associated with cerebrospinal fluid biomarkers for AD and a common intergenic variant found near the TREML2 gene has been identified to be protective for AD. However, little is known about the functional variant underlying the latter association or its relationship with the p. R47H. Here, we report comprehensive analyses using whole-exome sequencing data, cerebrospinal fluid biomarker analyses, meta-analyses (16,254 cases and 20,052 controls) and cell-based functional studies to support the role of the TREML2 coding missense variant p. S144G (rs3747742) as a potential driver of the metaanalysis AD-associated genome-wide association studies signal. Additionally, we demonstrate that the protective role of TREML2 in AD is independent of the role of TREM2 gene as a risk factor for AD. (C) 2014 Elsevier Inc. All rights reserved.
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