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Genome-wide pleiotropy analysis of neuropathological traits related to Alzheimer’s disease

Overview of attention for article published in Alzheimer's Research & Therapy, February 2018
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Mentioned by

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5 tweeters

Citations

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20 Dimensions

Readers on

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42 Mendeley
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Title
Genome-wide pleiotropy analysis of neuropathological traits related to Alzheimer’s disease
Published in
Alzheimer's Research & Therapy, February 2018
DOI 10.1186/s13195-018-0349-z
Pubmed ID
29458411
Authors

Jaeyoon Chung, Xiaoling Zhang, Mariet Allen, Xue Wang, Yiyi Ma, Gary Beecham, Thomas J. Montine, Steven G. Younkin, Dennis W. Dickson, Todd E. Golde, Nathan D. Price, Nilüfer Ertekin-Taner, Kathryn L. Lunetta, Jesse Mez, Richard Mayeux, Jonathan L. Haines, Margaret A. Pericak-Vance, Gerard Schellenberg, Gyungah R. Jun, Lindsay A. Farrer

Abstract

Simultaneous consideration of two neuropathological traits related to Alzheimer's disease (AD) has not been attempted in a genome-wide association study. We conducted genome-wide pleiotropy analyses using association summary statistics from the Beecham et al. study (PLoS Genet 10:e1004606, 2014) for AD-related neuropathological traits, including neuritic plaque (NP), neurofibrillary tangle (NFT), and cerebral amyloid angiopathy (CAA). Significant findings were further examined by expression quantitative trait locus and differentially expressed gene analyses in AD vs. control brains using gene expression data. Genome-wide significant pleiotropic associations were observed for the joint model of NP and NFT (NP + NFT) with the single-nucleotide polymorphism (SNP) rs34487851 upstream of C2orf40 (alias ECRG4, P = 2.4 × 10-8) and for the joint model of NFT and CAA (NFT + CAA) with the HDAC9 SNP rs79524815 (P = 1.1 × 10-8). Gene-based testing revealed study-wide significant associations (P ≤ 2.0 × 10-6) for the NFT + CAA outcome with adjacent genes TRAPPC12, TRAPPC12-AS1, and ADI1. Risk alleles of proxy SNPs for rs79524815 were associated with significantly lower expression of HDAC9 in the brain (P = 3.0 × 10-3), and HDAC9 was significantly downregulated in subjects with AD compared with control subjects in the prefrontal (P = 7.9 × 10-3) and visual (P = 5.6 × 10-4) cortices. Our findings suggest that pleiotropy analysis is a useful approach to identifying novel genetic associations with complex diseases and their endophenotypes. Functional studies are needed to determine whether ECRG4 or HDAC9 is plausible as a therapeutic target.

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Twitter Demographics

The data shown below were collected from the profiles of 5 tweeters who shared this research output. Click here to find out more about how the information was compiled.

Mendeley readers

The data shown below were compiled from readership statistics for 42 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 42 100%

Demographic breakdown

Readers by professional status Count As %
Researcher 9 21%
Student > Ph. D. Student 4 10%
Student > Bachelor 3 7%
Professor 3 7%
Professor > Associate Professor 3 7%
Other 7 17%
Unknown 13 31%
Readers by discipline Count As %
Biochemistry, Genetics and Molecular Biology 9 21%
Neuroscience 6 14%
Medicine and Dentistry 5 12%
Agricultural and Biological Sciences 3 7%
Mathematics 1 2%
Other 5 12%
Unknown 13 31%

Attention Score in Context

This research output has an Altmetric Attention Score of 3. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 06 March 2018.
All research outputs
#13,065,845
of 23,023,224 outputs
Outputs from Alzheimer's Research & Therapy
#1,083
of 1,244 outputs
Outputs of similar age
#161,062
of 331,055 outputs
Outputs of similar age from Alzheimer's Research & Therapy
#21
of 35 outputs
Altmetric has tracked 23,023,224 research outputs across all sources so far. This one is in the 42nd percentile – i.e., 42% of other outputs scored the same or lower than it.
So far Altmetric has tracked 1,244 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 25.9. This one is in the 12th percentile – i.e., 12% of its peers scored the same or lower than it.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 331,055 tracked outputs that were published within six weeks on either side of this one in any source. This one has gotten more attention than average, scoring higher than 50% of its contemporaries.
We're also able to compare this research output to 35 others from the same source and published within six weeks on either side of this one. This one is in the 40th percentile – i.e., 40% of its contemporaries scored the same or lower than it.

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