| 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 |
| Authors: |
Carrasquillo, MM; Allen, M; Burgess, JD; Wang, X; Strickland, SL; Aryal, S; Siuda, J; Kachadoorian, ML; Medway, C; Younkin, CS; Nair, A; Wang, C; Chanana, P; Serie, D; Nguyen, T; Lincoln, S; Malphrus, KG; Morgan, K; Golde, TE; Price, ND; White, CC; De Jager, PL; Bennett, DA; Asmann, YW; Crook, JE; Petersen, RC; Graff-Radford, NR; Dickson, DW; Younkin, SG; Ertekin-Taner, N |
| Source: |
Alzheimer's & Dementia , 13 (6) pp. 663-673. (2017) |
| Publication Year: |
2017 |
| Collection: |
University College London: UCL Discovery |
| Subject Terms: |
Alzheimer's disease; Regulatory variant; TREM2; TREML1; eQTL; 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 |
| Description: |
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. |
| Document Type: |
article in journal/newspaper |
| File Description: |
text |
| Language: |
English |
| Relation: |
https://discovery.ucl.ac.uk/id/eprint/10057513/ |
| Availability: |
https://discovery.ucl.ac.uk/id/eprint/10057513/7/Louro%20Guerreiro_2016_Carrasquillo_etal_TREM_ADJ-D-16-00130R1Segment%20001.pdf; https://discovery.ucl.ac.uk/id/eprint/10057513/ |
| Rights: |
open |
| Accession Number: |
edsbas.8D33A272 |
| Database: |
BASE |