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Brain Expression Genome-Wide Association Study (eGWAS) Identifies Human Disease-Associated Variants

Overview of attention for article published in PLoS Genetics, June 2012
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  • In the top 25% of all research outputs scored by Altmetric
  • High Attention Score compared to outputs of the same age (89th percentile)
  • High Attention Score compared to outputs of the same age and source (81st percentile)

Mentioned by

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1 news outlet
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4 X users
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2 Facebook pages

Citations

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208 Dimensions

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279 Mendeley
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6 CiteULike
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Title
Brain Expression Genome-Wide Association Study (eGWAS) Identifies Human Disease-Associated Variants
Published in
PLoS Genetics, June 2012
DOI 10.1371/journal.pgen.1002707
Pubmed ID
Authors

Fanggeng Zou, High Seng Chai, Curtis S. Younkin, Mariet Allen, Julia Crook, V. Shane Pankratz, Minerva M. Carrasquillo, Christopher N. Rowley, Asha A. Nair, Sumit Middha, Sooraj Maharjan, Thuy Nguyen, Li Ma, Kimberly G. Malphrus, Ryan Palusak, Sarah Lincoln, Gina Bisceglio, Constantin Georgescu, Naomi Kouri, Christopher P. Kolbert, Jin Jen, Jonathan L. Haines, Richard Mayeux, Margaret A. Pericak-Vance, Lindsay A. Farrer, Gerard D. Schellenberg, Ronald C. Petersen, Neill R. Graff-Radford, Dennis W. Dickson, Steven G. Younkin, Nilüfer Ertekin-Taner

Abstract

Genetic variants that modify brain gene expression may also influence risk for human diseases. We measured expression levels of 24,526 transcripts in brain samples from the cerebellum and temporal cortex of autopsied subjects with Alzheimer's disease (AD, cerebellar n=197, temporal cortex n=202) and with other brain pathologies (non-AD, cerebellar n=177, temporal cortex n=197). We conducted an expression genome-wide association study (eGWAS) using 213,528 cisSNPs within ± 100 kb of the tested transcripts. We identified 2,980 cerebellar cisSNP/transcript level associations (2,596 unique cisSNPs) significant in both ADs and non-ADs (q<0.05, p=7.70 × 10(-5)-1.67 × 10(-82)). Of these, 2,089 were also significant in the temporal cortex (p=1.85 × 10(-5)-1.70 × 10(-141)). The top cerebellar cisSNPs had 2.4-fold enrichment for human disease-associated variants (p<10(-6)). We identified novel cisSNP/transcript associations for human disease-associated variants, including progressive supranuclear palsy SLCO1A2/rs11568563, Parkinson's disease (PD) MMRN1/rs6532197, Paget's disease OPTN/rs1561570; and we confirmed others, including PD MAPT/rs242557, systemic lupus erythematosus and ulcerative colitis IRF5/rs4728142, and type 1 diabetes mellitus RPS26/rs1701704. In our eGWAS, there was 2.9-3.3 fold enrichment (p<10(-6)) of significant cisSNPs with suggestive AD-risk association (p<10(-3)) in the Alzheimer's Disease Genetics Consortium GWAS. These results demonstrate the significant contributions of genetic factors to human brain gene expression, which are reliably detected across different brain regions and pathologies. The significant enrichment of brain cisSNPs among disease-associated variants advocates gene expression changes as a mechanism for many central nervous system (CNS) and non-CNS diseases. Combined assessment of expression and disease GWAS may provide complementary information in discovery of human disease variants with functional implications. Our findings have implications for the design and interpretation of eGWAS in general and the use of brain expression quantitative trait loci in the study of human disease genetics.

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Geographical breakdown

Country Count As %
United States 10 4%
Germany 2 <1%
Spain 2 <1%
Brazil 2 <1%
Norway 1 <1%
Italy 1 <1%
United Kingdom 1 <1%
Unknown 260 93%

Demographic breakdown

Readers by professional status Count As %
Researcher 72 26%
Student > Ph. D. Student 52 19%
Other 19 7%
Student > Master 19 7%
Professor 18 6%
Other 59 21%
Unknown 40 14%
Readers by discipline Count As %
Agricultural and Biological Sciences 95 34%
Biochemistry, Genetics and Molecular Biology 43 15%
Medicine and Dentistry 31 11%
Neuroscience 23 8%
Computer Science 13 5%
Other 23 8%
Unknown 51 18%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 12. 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 29 October 2021.
All research outputs
#3,086,892
of 25,411,814 outputs
Outputs from PLoS Genetics
#2,565
of 8,964 outputs
Outputs of similar age
#19,752
of 180,819 outputs
Outputs of similar age from PLoS Genetics
#29
of 161 outputs
Altmetric has tracked 25,411,814 research outputs across all sources so far. Compared to these this one has done well and is in the 87th percentile: it's in the top 25% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 8,964 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 17.8. This one has gotten more attention than average, scoring higher than 71% of its peers.
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 180,819 tracked outputs that were published within six weeks on either side of this one in any source. This one has done well, scoring higher than 89% of its contemporaries.
We're also able to compare this research output to 161 others from the same source and published within six weeks on either side of this one. This one has done well, scoring higher than 81% of its contemporaries.