DESCRIPTION:

List of positional candidate genes after correcting for multiple testing and controlling the false discovery rate from genome wide association studies (GWAS) retrieved from the NHGRI-EBI Catalog of published genome-wide association studies (http://www.ebi.ac.uk/gwas/). The disease/trait examined in this study, as reported by the authors, was Longitudinal change in brain amyloid plaque burden. The EFO term amyloid plaque accumulation rate was annotated to this set after curation by NHGRI-EBI. Intergenic SNPS were mapped to both the upstream and downstream gene. P-value uploaded. This gene set was generated using gwas2gs v. 0.1.8 and the GWAS Catalog v. 1.0.1.

LABEL:

GWAS: amyloid plaque accumulation rate

SCORE TYPE:

P-Value

DATE ADDED:

2017-05-02

DATE UPDATED:

2024-04-25

SPECIES:

AUTHORS:

VK Ramanan, SL Risacher, K Nho, S Kim, L Shen, BC McDonald, KK Yoder, GD Hutchins, JD West, EF Tallman, S Gao, TM Foroud, MR Farlow, PL De Jager, DA Bennett, PS Aisen, RC Petersen, CR Jack, AW Toga, RC Green, WJ Jagust, MW Weiner, AJ Saykin

TITLE:

GWAS of longitudinal amyloid accumulation on 18F-florbetapir PET in Alzheimer's disease implicates microglial activation gene IL1RAP.

JOURNAL:

Brain : a journal of neurology Oct 2015, Vol 138, pp. 3076-88

ABSTRACT:

Brain amyloid deposition is thought to be a seminal event in Alzheimer's disease. To identify genes influencing Alzheimer's disease pathogenesis, we performed a genome-wide association study of longitudinal change in brain amyloid burden measured by (18)F-florbetapir PET. A novel association with higher rates of amyloid accumulation independent from APOE (apolipoprotein E) ε4 status was identified in IL1RAP (interleukin-1 receptor accessory protein; rs12053868-G; P = 1.38 × 10(-9)) and was validated by deep sequencing. IL1RAP rs12053868-G carriers were more likely to progress from mild cognitive impairment to Alzheimer's disease and exhibited greater longitudinal temporal cortex atrophy on MRI. In independent cohorts rs12053868-G was associated with accelerated cognitive decline and lower cortical (11)C-PBR28 PET signal, a marker of microglial activation. These results suggest a crucial role of activated microglia in limiting amyloid accumulation and nominate the IL-1/IL1RAP pathway as a potential target for modulating this process. PUBMED: 26268530
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