↓ Skip to main content

Early-Onset Alzheimer Disease and Candidate Risk Genes Involved in Endolysosomal Transport.

Overview of attention for article published in JAMA Neurology, September 2017
Altmetric Badge

About this Attention Score

  • In the top 5% of all research outputs scored by Altmetric
  • High Attention Score compared to outputs of the same age (94th percentile)
  • Above-average Attention Score compared to outputs of the same age and source (52nd percentile)

Mentioned by

news
3 news outlets
twitter
31 X users
facebook
4 Facebook pages
googleplus
1 Google+ user

Citations

dimensions_citation
40 Dimensions

Readers on

mendeley
170 Mendeley
You are seeing a free-to-access but limited selection of the activity Altmetric has collected about this research output. Click here to find out more.
Title
Early-Onset Alzheimer Disease and Candidate Risk Genes Involved in Endolysosomal Transport.
Published in
JAMA Neurology, September 2017
DOI 10.1001/jamaneurol.2017.1518
Pubmed ID
Authors

Brian W Kunkle, Badri N Vardarajan, Adam C Naj, Patrice L Whitehead, Sophie Rolati, Susan Slifer, Regina M Carney, Michael L Cuccaro, Jeffery M Vance, John R Gilbert, Li-San Wang, Lindsay A Farrer, Christiane Reitz, Jonathan L Haines, Gary W Beecham, Eden R Martin, Gerard D Schellenberg, Richard P Mayeux, Margaret A Pericak-Vance

Abstract

Mutations in APP, PSEN1, and PSEN2 lead to early-onset Alzheimer disease (EOAD) but account for only approximately 11% of EOAD overall, leaving most of the genetic risk for the most severe form of Alzheimer disease unexplained. This extreme phenotype likely harbors highly penetrant risk variants, making it primed for discovery of novel risk genes and pathways for AD. To search for rare variants contributing to the risk for EOAD. In this case-control study, whole-exome sequencing (WES) was performed in 51 non-Hispanic white (NHW) patients with EOAD (age at onset <65 years) and 19 Caribbean Hispanic families previously screened as negative for established APP, PSEN1, and PSEN2 causal variants. Participants were recruited from John P. Hussman Institute for Human Genomics, Case Western Reserve University, and Columbia University. Rare, deleterious, nonsynonymous, or loss-of-function variants were filtered to identify variants in known and suspected AD genes, variants in multiple unrelated NHW patients, variants present in 19 Hispanic EOAD WES families, and genes with variants in multiple unrelated NHW patients. These variants/genes were tested for association in an independent cohort of 1524 patients with EOAD, 7046 patients with late-onset AD (LOAD), and 7001 cognitively intact controls (age at examination, >65 years) from the Alzheimer's Disease Genetics Consortium. The study was conducted from January 21, 2013, to October 13, 2016. Alzheimer disease diagnosed according to standard National Institute of Neurological and Communicative Disorders and Stroke and the Alzheimer Disease and Related Disorders Association criteria. Association between Alzheimer disease and genetic variants and genes was measured using logistic regression and sequence kernel association test-optimal gene tests, respectively. Of the 1524 NHW patients with EOAD, 765 (50.2%) were women and mean (SD) age was 60.0 (4.9) years; of the 7046 NHW patients with LOAD, 4171 (59.2%) were women and mean (SD) age was 77.4 (8.6) years; and of the 7001 NHW controls, 4215 (60.2%) were women and mean (SD) age was 77.4 (8.6) years. The gene PSD2, for which multiple unrelated NHW cases had rare missense variants, was significantly associated with EOAD (P = 2.05 × 10-6; Bonferroni-corrected P value [BP] = 1.3 × 10-3) and LOAD (P = 6.22 × 10-6; BP = 4.1 × 10-3). A missense variant in TCIRG1, present in a NHW patient and segregating in 3 cases of a Hispanic family, was more frequent in EOAD cases (odds ratio [OR], 2.13; 95% CI, 0.99-4.55; P = .06; BP = 0.413), and significantly associated with LOAD (OR, 2.23; 95% CI, 1.37-3.62; P = 7.2 × 10-4; BP = 5.0 × 10-3). A missense variant in the LOAD risk gene RIN3 showed suggestive evidence of association with EOAD after Bonferroni correction (OR, 4.56; 95% CI, 1.26-16.48; P = .02, BP = 0.091). In addition, a missense variant in RUFY1 identified in 2 NHW EOAD cases showed suggestive evidence of an association with EOAD as well (OR, 18.63; 95% CI, 1.62-213.45; P = .003; BP = 0.129). The genes PSD2, TCIRG1, RIN3, and RUFY1 all may be involved in endolysosomal transport-a process known to be important to development of AD. Furthermore, this study identified shared risk genes between EOAD and LOAD similar to previously reported genes, such as SORL1, PSEN2, and TREM2.

X Demographics

X Demographics

The data shown below were collected from the profiles of 31 X users who shared this research output. Click here to find out more about how the information was compiled.
Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 170 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 170 100%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 32 19%
Researcher 27 16%
Student > Master 12 7%
Student > Bachelor 11 6%
Student > Doctoral Student 8 5%
Other 27 16%
Unknown 53 31%
Readers by discipline Count As %
Medicine and Dentistry 25 15%
Biochemistry, Genetics and Molecular Biology 24 14%
Neuroscience 22 13%
Agricultural and Biological Sciences 14 8%
Psychology 7 4%
Other 20 12%
Unknown 58 34%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 44. 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 17 June 2023.
All research outputs
#948,416
of 25,382,440 outputs
Outputs from JAMA Neurology
#1,143
of 5,847 outputs
Outputs of similar age
#19,321
of 324,453 outputs
Outputs of similar age from JAMA Neurology
#32
of 68 outputs
Altmetric has tracked 25,382,440 research outputs across all sources so far. Compared to these this one has done particularly well and is in the 96th percentile: it's in the top 5% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 5,847 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 44.2. This one has done well, scoring higher than 80% 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 324,453 tracked outputs that were published within six weeks on either side of this one in any source. This one has done particularly well, scoring higher than 94% of its contemporaries.
We're also able to compare this research output to 68 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 52% of its contemporaries.