Evidence map›Paper›PMID 26339675›Full record

ArticleAnnals of clinical and translational neurology2015

F-box/LRR-repeat protein 7 is genetically associated with Alzheimer's disease.

Giuseppe Tosto, Hongjun Fu, Badri N Vardarajan, Joseph H Lee, Rong Cheng, Dolly Reyes-Dumeyer, Rafael Lantigua, Martin Medrano, Ivonne Z Jimenez-Velazquez, Mitchell S V Elkind and 8 more

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Annals of clinical and translational neurology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers, 7 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
42citing papers in PubMed, 7 pooled it
4.0field-weighted citation impact, top 6% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

42 citing papers in PubMed, 7 syntheses or guidelines pooled it, 74 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Pooled it
  4. Pooled it
  5. Pooled it
  6. Pooled it
  7. Pooled it
  8. Review
  9. Article
  10. RBFOX1 association with age at onset of Alzheimer's disease.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026
    Article
  11. Article
  12. APOE and Alzheimer's disease and related dementias risk among 12,221 Hispanics/Latinos.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025
    Article
  13. Review
  14. Whole-genome sequencing study in Koreans identifies novel loci for Alzheimer's disease.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2024
    Article
  15. Connecting genomic and proteomic signatures of amyloid burden in the brain.medRxiv : the preprint server for health sciences · 2024
    Article
  16. Article
  17. Article
  18. Article
  19. The Early-Onset Alzheimer's Disease Whole-Genome Sequencing Project: Study design and methodology.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2023
    Article
  20. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

18 authors at 7 institutions in 5 countries.

Giuseppe TostoThe Taub Institute for Research on Alzheimer's Disease and the Aging Brain, School of Public Health, Columbia University New York, New York ; The Gertrude H. Sergievsky Center, School of Public Health, Columbia University New York, New York.
Hongjun FuThe Taub Institute for Research on Alzheimer's Disease and the Aging Brain, School of Public Health, Columbia University New York, New York.
Badri N VardarajanThe Taub Institute for Research on Alzheimer's Disease and the Aging Brain, School of Public Health, Columbia University New York, New York ; The Gertrude H. Sergievsky Center, School of Public Health, Columbia University New York, New York.
Joseph H LeeThe Taub Institute for Research on Alzheimer's Disease and the Aging Brain, School of Public Health, Columbia University New York, New York ; The Gertrude H. Sergievsky Center, School of Public Health, Columbia University New York, New York.
Rong ChengThe Taub Institute for Research on Alzheimer's Disease and the Aging Brain, School of Public Health, Columbia University New York, New York ; The Gertrude H. Sergievsky Center, School of Public Health, Columbia University New York, New York.
Dolly Reyes-DumeyerThe Taub Institute for Research on Alzheimer's Disease and the Aging Brain, School of Public Health, Columbia University New York, New York ; The Gertrude H. Sergievsky Center, School of Public Health, Columbia University New York, New York.
Rafael LantiguaDepartment of Medicine College of Physicians and Surgeons, School of Public Health, Columbia University New York, New York.
Martin MedranoSchool of Medicine, Pontificia Universidad Catolica Madre y Maestra Santiago, Dominican Republic.
Ivonne Z Jimenez-VelazquezDepartment of Medicine, Geriatrics Program, School of Medicine, University of Puerto Rico San Juan, Puerto Rico.
Mitchell S V ElkindThe Gertrude H. Sergievsky Center, School of Public Health, Columbia University New York, New York ; Department of Neurology, Columbia University New York, New York.
Clinton B WrightEvelyn F. McKnight Brain Institute and Departments of Neurology, Public Health Sciences, John T. McDonald Department of Human Genetics, University of Miami Miami, Florida, 33136.
Ralph L SaccoEvelyn F. McKnight Brain Institute and Departments of Neurology, Public Health Sciences, John T. McDonald Department of Human Genetics, University of Miami Miami, Florida, 33136 ; Neuroscience Program, Leonard M. Miller School of Medicine, University of Miami Miami, Florida, 33136.
Margaret Pericak-VanceNeuroscience Program, Leonard M. Miller School of Medicine, University of Miami Miami, Florida, 33136 ; The John P. Hussman Institute for Human Genomics, University of Miami Miami, Florida, 33136.
Lindsay FarrerDepartments of Medicine (Biomedical Genetics), Neurology, Ophthalmology, Biostatistics and Epidemiology, Boston University Schools of Medicine and Public Health Boston, Massachusetts.
Ekaterina RogaevaTanz Centre for Research in Neurodegenerative Diseases, and Department of Medicine, University of Toronto Krembil Discovery Tower, 60 Leonard Avenue, Toronto, Ontario, Canada, M5T 2S8.
Peter St George-HyslopTanz Centre for Research in Neurodegenerative Diseases, and Department of Medicine, University of Toronto Krembil Discovery Tower, 60 Leonard Avenue, Toronto, Ontario, Canada, M5T 2S8 ; Department of Clinical Neurosciences, Cambridge Institute for Medical Research, University of Cambridge Cambridge, CB2 0XY, United Kingdom.
Christiane ReitzThe Taub Institute for Research on Alzheimer's Disease and the Aging Brain, School of Public Health, Columbia University New York, New York ; The Gertrude H. Sergievsky Center, School of Public Health, Columbia University New York, New York ; Department of Neurology, Columbia University New York, New York.
Richard MayeuxThe Taub Institute for Research on Alzheimer's Disease and the Aging Brain, School of Public Health, Columbia University New York, New York ; The Gertrude H. Sergievsky Center, School of Public Health, Columbia University New York, New York ; Department of Neurology, Columbia University New York, New York ; Department of Psychiatry, School of Public Health, Columbia University New York, New York ; Department of Epidemiology, School of Public Health, Columbia University New York, New York.
Columbia University · USUniversity of Miami · USBoston Public Schools · USPontificia Universidad Católica Madre y Maestra · DOUniversity of Cambridge · GBUniversity of Puerto Rico System · PRUniversity of Toronto · CA

Funding

Satellite Diagnostic and Treatment Clinic CoreP50AG008702 · NIA · COLUMBIA UNIV NEW YORK MORNINGSIDE · PI DE JAGER, PHILIP L · 1989 to 2019
$46.3M
The National Institute on Aging (NIA) Late Onset of Alzheimer's Disease (LOAD) Family-Based Study (FBS)U24AG056270 · NIA · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI Gary Wayne Beecham, TATIANA M. FOROUD · 2017 to 2026
$31.4M
STROKE INCIDENCE AND RISK FACTORS IN A TRI-ETHNIC REGIONR01NS029993 · NINDS · UNIVERSITY OF MIAMI SCHOOL OF MEDICINE · PI ELKIND, MITCHELL S, SACCO, RALPH L. · 1993 to 2019
$19.2M
Stroke Incidence and Risk Factors in a Tri-Ethnic RegionR37NS029993 · NINDS · UNIVERSITY OF MIAMI SCHOOL OF MEDICINE · PI ELKIND, MITCHELL S, SACCO, RALPH L. · 2008 to 2014
$12.1M
Genetic Epidemiology of Alzheimer's Disease in HispanicsR37AG015473 · NIA · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI MAYEUX, RICHARD P · 2004 to 2013
$10.8M
Epidemiology of Biomarkers of Risk and Progression in LOADR01AG037212 · NIA · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI MAYEUX, RICHARD P, SCHUPF, NICOLE · 2010 to 2015
$10.1M
Epidemiology of Familial Late-Onset Alzheimer's DiseaseR01AG041797 · NIA · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI MAYEUX, RICHARD P · 2012 to 2016
$4.2M
Genetic Studies of Alzheimer's Disease in Caribbean HispanicsRF1AG015473 · NIA · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI MAYEUX, RICHARD P · 2015 to 2018
$3.3M
Medical Research Council MC_G1000734NIA NIH HHS P50 AG008702NIA NIH HHS R01 AG037212NIA NIH HHS R01 AG041797NIA NIH HHS R37 AG015473NIA NIH HHS RF1 AG015473NIA NIH HHS U24 AG056270NINDS NIH HHS R01 NS029993NINDS NIH HHS R37 NS029993Wellcome Trust 081864Wellcome Trust 089703
6 · The paper itself

Abstract

objectiveIn the context of late-onset Alzheimer's disease (LOAD) over 20 genes have been identified but, aside APOE, all show small effect sizes, leaving a large part of the genetic component unexplained. Admixed populations, such as Caribbean Hispanics, can provide a valuable contribution because of their unique genetic profile and higher incidence of the disease. We aimed to identify novel loci associated with LOAD.

methodsAbout 4514 unrelated Caribbean Hispanics (2451 cases and 2063 controls) were selected for genome-wide association analysis. Significant loci were further tested in the expanded cohort that also included related family members (n = 5300). Two AD-like transgenic mice models (J20 and rTg4510) were used to study gene expression. Independent data sets of non-Hispanic Whites and African Americans were used to further validate findings, along with publicly available brain expression data sets.

resultsA novel locus, rs75002042 in FBXL7 (5p15.1), was found genome-wide significant in the case-control cohort (odd ratio [OR] = 0.61, P = 6.19E-09) and confirmed in the related members cohorts (OR = 0.63, P = 4.7E-08). Fbxl7 protein was overexpressed in both AD-like transgenic mice compared to wild-type littermates. Publicly available microarray studies also showed significant overexpression of Fbxl7 in LOAD brains compared to nondemented controls. single-nucleotide polymorphism (SNP) rs75002042 was in complete linkage disequilibrium with other variants in two independent non-Hispanic White and African American data sets (0.0005 < P < 0.02) used for replication.

interpretationFBXL7, encodes a subcellular protein involved in phosphorylation-dependent ubiquitination processes and displays proapoptotic activity. F-box proteins also modulate inflammation and innate immunity, which may be important in LOAD pathogenesis. Further investigations are needed to validate and understand its role in this and other populations.

Identifiers

PMID26339675
PMCPMC4554442
OpenAlexW1716810435

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.