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Genetic variation at 16q24.2 is associated with small vessel stroke

Overview of attention for article published in Annals of Neurology, March 2017
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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 (81st percentile)
  • Above-average Attention Score compared to outputs of the same age and source (64th percentile)

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Title
Genetic variation at 16q24.2 is associated with small vessel stroke
Published in
Annals of Neurology, March 2017
DOI 10.1002/ana.24840
Pubmed ID
Authors

Matthew Traylor, Rainer Malik, Mike A. Nalls, Ioana Cotlarciuc, Farid Radmanesh, Gudmar Thorleifsson, Ken B. Hanscombe, Carl Langefeld, Danish Saleheen, Natalia S. Rost, Idil Yet, Tim D. Spector, Jordana T. Bell, Eilis Hannon, Jonathan Mill, Ganesh Chauhan, Stephanie Debette, Joshua C. Bis, W.T. Longstreth, M. Arfan Ikram, Lenore J. Launer, Sudha Seshadri, Young Lacunar DNA Study METASTROKE, Monica Anne Hamilton‐Bruce, Jordi Jimenez‐Conde, John W. Cole, Reinhold Schmidt, Agnieszka Słowik, Robin Lemmens, Arne Lindgren, Olle Melander, Raji P. Grewal, Ralph L. Sacco, Tatjana Rundek, Kathryn Rexrode, Donna K. Arnett, Julie A. Johnson, Oscar R. Benavente, Sylvia Wasssertheil‐Smoller, Jin‐Moo Lee, Sara L. Pulit, Quenna Wong, Stephen S. Rich, Paul I.W. de Bakker, Patrick F. McArdle, Daniel Woo, Christopher D. Anderson, Huichun Xu, Laura Heitsch, Myriam Fornage, Christina Jern, Kari Stefansson, Unnur Thorsteinsdottir, Solveig Gretarsdottir, Cathryn M. Lewis, Pankaj Sharma, Cathie L.M. Sudlow, Peter M. Rothwell, Giorgio B. Boncoraglio, Vincent Thijs, Chris Levi, James F. Meschia, Jonathan Rosand, Steven J. Kittner, Braxton D. Mitchell, Martin Dichgans, Bradford B. Worrall, Hugh S. Markus, on behalf of the International Stroke Genetics Consortium

Abstract

Genome-wide association studies (GWAS) have been successful at identifying associations with stroke and stroke subtypes, but have not yet identified any associations solely with small vessel stroke (SVS). SVS comprises a quarter of all ischaemic stroke and is a major manifestation of cerebral small vessel disease, the primary cause of vascular cognitive impairment. Studies across neurological traits have shown younger onset cases have an increased genetic burden. We leveraged this increased genetic burden by performing an age-at-onset informed GWAS meta-analysis, including a large younger onset SVS population, to identify novel associations with stroke. We used a three-stage age-at-onset informed GWAS to identify novel genetic variants associated with stroke. On identifying a novel locus associated with SVS, we assessed its influence on other small vessel disease phenotypes, as well as on mRNA expression of nearby genes, and on DNA methylation of nearby CpG sites in whole blood and in the fetal brain. We identified an association with SVS in 4,203 cases and 50,728 controls on chromosome 16q24.2 (OR(95% CI)=1.16(1.10-1.22); p=3.2x10(-9) ). The lead SNP (rs12445022) was also associated with cerebral white matter hyperintensities (OR(95% CI)=1.10(1.05-1.16); p=5.3x10(-5) ; N=3,670), but not intracerebral haemorrhage (OR(95% CI)=0.97(0.84-1.12); p=0.71; 1,545 cases, 1,481 controls). rs12445022 is associated with mRNA expression of ZCCHC14 in arterial tissues (p=9.4x10(-7) ), and DNA methylation at probe cg16596957 in whole blood (p=5.3x10(-6) ). 16q24.2 is associated with SVS. Associations of the locus with expression of ZCCHC14 and DNA methylation suggest the locus acts through changes to regulatory elements. This article is protected by copyright. All rights reserved.

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Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 121 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
United States 1 <1%
Unknown 120 99%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 20 17%
Researcher 20 17%
Student > Master 14 12%
Student > Bachelor 10 8%
Student > Doctoral Student 6 5%
Other 26 21%
Unknown 25 21%
Readers by discipline Count As %
Medicine and Dentistry 33 27%
Biochemistry, Genetics and Molecular Biology 11 9%
Neuroscience 11 9%
Nursing and Health Professions 10 8%
Agricultural and Biological Sciences 5 4%
Other 17 14%
Unknown 34 28%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 11. 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 02 July 2017.
All research outputs
#3,439,911
of 25,545,162 outputs
Outputs from Annals of Neurology
#1,590
of 5,599 outputs
Outputs of similar age
#59,880
of 323,246 outputs
Outputs of similar age from Annals of Neurology
#15
of 42 outputs
Altmetric has tracked 25,545,162 research outputs across all sources so far. Compared to these this one has done well and is in the 86th percentile: it's in the top 25% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 5,599 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 15.9. 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 323,246 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 81% of its contemporaries.
We're also able to compare this research output to 42 others from the same source and published within six weeks on either side of this one. This one has gotten more attention than average, scoring higher than 64% of its contemporaries.