Carrasquillo, MM;
Allen, M;
Burgess, JD;
Wang, X;
Strickland, SL;
Aryal, S;
Siuda, J;
... Ertekin-Taner, N; + view all
(2017)
A candidate regulatory variant at the TREM gene cluster associates with decreased Alzheimer's disease risk and increased TREML1 and TREM2 brain gene expression.
Alzheimer's & Dementia
, 13
(6)
pp. 663-673.
10.1016/j.jalz.2016.10.005.
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Louro Guerreiro_2016_Carrasquillo_etal_TREM_ADJ-D-16-00130R1Segment 001.pdf - Accepted Version Download (2MB) | Preview |
Abstract
INTRODUCTION: We hypothesized that common Alzheimer's disease (AD)-associated variants within the triggering receptor expressed on myeloid (TREM) gene cluster influence disease through gene expression. METHODS: Expression microarrays on temporal cortex and cerebellum from ∼400 neuropathologically diagnosed subjects and two independent RNAseq replication cohorts were used for expression quantitative trait locus analysis. RESULTS: A variant within a DNase hypersensitive site 5' of TREM2, rs9357347-C, associates with reduced AD risk and increased TREML1 and TREM2 levels (uncorrected P = 6.3 × 10-3 and 4.6 × 10-2, respectively). Meta-analysis on expression quantitative trait locus results from three independent data sets (n = 1006) confirmed these associations (uncorrected P = 3.4 × 10-2 and 3.5 × 10-3, Bonferroni-corrected P = 6.7 × 10-2 and 7.1 × 10-3, respectively). DISCUSSION: Our findings point to rs9357347 as a functional regulatory variant that contributes to a protective effect observed at the TREM locus in the International Genomics of Alzheimer's Project genome-wide association study meta-analysis and suggest concomitant increase in TREML1 and TREM2 brain levels as a potential mechanism for protection from AD.
| Type: | Article |
|---|---|
| Title: | A candidate regulatory variant at the TREM gene cluster associates with decreased Alzheimer's disease risk and increased TREML1 and TREM2 brain gene expression |
| Location: | United States |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1016/j.jalz.2016.10.005 |
| Publisher version: | http://dx.doi.org/10.1016/j.jalz.2016.10.005 |
| Language: | English |
| Additional information: | This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions. |
| Keywords: | Alzheimer's disease, Regulatory variant, TREM2, TREML1, eQTL, Aged, Aged, 80 and over, Alzheimer Disease, Cerebellum, Female, Gene Expression, Genetic Predisposition to Disease, Genetic Variation, Humans, Linkage Disequilibrium, Male, Membrane Glycoproteins, Microarray Analysis, Multigene Family, Quantitative Trait Loci, Receptors, Immunologic, Temporal Lobe |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Neurodegenerative Diseases |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10057513 |
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