A candidate regulatory variant at the TREM gene cluster associates with decreased Alzheimer's disease risk and increased TREML1 and TREM2 brain gene expression.
Publication Title
Alzheimers Dement
Document Type
Article
Publication Date
6-1-2017
Keywords
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
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
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.
Clinical Institute
Neurosciences (Brain & Spine)
Specialty/Research Institute
Geriatrics
Specialty/Research Institute
Neurosciences
