ArticleNeurobiology of aging2016
Discovery of gene-gene interactions across multiple independent data sets of late onset Alzheimer disease from the Alzheimer Disease Genetics Consortium.
Abstract read
In one paragraph
Article in Neurobiology of aging, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers, 2 of them syntheses that pooled it.
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25citing papers in PubMed, 2 pooled it
4.3field-weighted citation impact, top 5% of its field
What it found
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The trial behind it
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Who cites it
25 citing papers in PubMed, 2 syntheses or guidelines pooled it, 58 citations in OpenAlex.
- Pooled it
- Association of CD14-260 (-159) C/T and Alzheimer's disease: systematic review and trial sequential analyses.Journal of neural transmission (Vienna, Austria : 1996) · 2018Pooled it
- Genotypic Effects of the TOMM40'523 Variant and APOE on Longitudinal Cognitive Change over 4 Years: The TOMMORROW Study.The journal of prevention of Alzheimer's disease · 2023Trial
- Omics-driven strategies for identifying biomarkers in Alzheimer's disease.Metabolic brain disease · 2026Review
- Prosaposin in CNS health and disease, metabolic stress and exercise adaptation.Journal of molecular medicine (Berlin, Germany) · 2026Review
- Gene interactions analysis of brain spatial transcriptome for Alzheimer's disease.Genes & diseases · 2024Article
- Revealing third-order interactions through the integration of machine learning and entropy methods in genomic studies.BioData mining · 2024Article
- Novel Alzheimer's disease genes and epistasis identified using machine learning GWAS platform.Scientific reports · 2023Article
- Downregulation of Sirtuin 1 Does Not Account for the Impaired Long-Term Potentiation in the Prefrontal Cortex of Female APPswe/PS1dE9 Mice Modelling Alzheimer's Disease.International journal of molecular sciences · 2023Article
- Whole Person Modeling: a transdisciplinary approach to mental health research.Discover mental health · 2023Review
- A comparison of methods for interpreting random forest models of genetic association in the presence of non-additive interactions.BioData mining · 2021Article
- The Critical Role of SIRT1 in Parkinson's Disease: Mechanism and Therapeutic Considerations.Aging and disease · 2020Review
- Loss of Cav1.2 channels impairs hippocampal theta burst stimulation-induced long-term potentiation.Channels (Austin, Tex.) · 2020Article
- Genetic architecture of Alzheimer's disease.Neurobiology of disease · 2020Review
- Synonymous variants associated with Alzheimer disease in multiplex families.Neurology. Genetics · 2020Article
- Genetic risk for coronary heart disease alters the influence of Alzheimer's genetic risk on mild cognitive impairment.Neurobiology of aging · 2019Article
- A statistical framework for cross-tissue transcriptome-wide association analysis.Nature genetics · 2019Article
- Early Life Stress and Epigenetics in Late-onset Alzheimer's Dementia: A Systematic Review.Current genomics · 2018Review
- Integrative genomic analysis of methylphenidate response in attention-deficit/hyperactivity disorder.Scientific reports · 2018Article
- Systems healthcare: a holistic paradigm for tomorrow.BMC systems biology · 2017Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
18 authors at 9 institutions in 1 country.
Timothy J HohmanVanderbilt Memory & Alzheimer's Center, Department of Neurology, Vanderbilt University Medical Center, Nashville, TN, USA.
William S BushDepartment of Epidemiology and Biostatistics, Case Western Reserve University, Cleveland, OH, USA.
Lan JiangVanderbilt Genetics Institute, Vanderbilt University Medical Center, Nashville, TN, USA.
Kristin D Brown-GentryVanderbilt Genetics Institute, Vanderbilt University Medical Center, Nashville, TN, USA.
Eric S TorstensonVanderbilt Genetics Institute, Vanderbilt University Medical Center, Nashville, TN, USA.
Scott M DudekVanderbilt Genetics Institute, Vanderbilt University Medical Center, Nashville, TN, USA.
Shubhabrata MukherjeeDepartment of Medicine, University of Washington, Seattle, WA, USA.
Adam NajDepartment of Biostatistics and Epidemiology, University of Pennsylvania, Philadelphia, PA, USA.
Brian W KunkleDr. John T. Macdonald Foundation Department of Human Genetics and John P. Hussman Institute for Human Genomics, Miller School of Medicine, University of Miami, Miami, FL, USA.
Marylyn D RitchieDepartment of Biochemistry and Molecular Biology, The Pennsylvania State University, University Park, PA, USA.
Eden R MartinDr. John T. Macdonald Foundation Department of Human Genetics and John P. Hussman Institute for Human Genomics, Miller School of Medicine, University of Miami, Miami, FL, USA; Department of Public Health Sciences, Miller School of Medicine, University of Miami, Miami, FL, USA.
Gerard D SchellenbergDepartment of Pathology and Laboratory Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.
Richard MayeuxGertrude H. Sergievsky Center, Department of Neurology and the Taub Institute for Research on Alzheimer's Disease and the Aging Brain, College of Physicians and Surgeons, Columbia University, New York, NY, USA.
Lindsay A FarrerDepartment of Medicine (Biomedical Genetics), Boston University, Boston, MA, USA; Department of Neurology, Boston University, Boston, MA, USA; Department of Ophthalmology, Boston University, Boston, MA, USA; Department of Epidemiology, Boston University, Boston, MA, USA; Department of Biostatistics, Boston University, Boston, MA, USA.
Margaret A Pericak-VanceDr. John T. Macdonald Foundation Department of Human Genetics and John P. Hussman Institute for Human Genomics, Miller School of Medicine, University of Miami, Miami, FL, USA; Department of Neurology, Miller School of Medicine, University of Miami, Miami, FL, USA.
Jonathan L HainesDepartment of Epidemiology and Biostatistics, Case Western Reserve University, Cleveland, OH, USA.
Tricia A Thornton-WellsVanderbilt Genetics Institute, Department of Molecular Physiology & Biophysics, Vanderbilt University Medical Center, Nashville, TN, USA. Electronic address: triciathorntonwells@gmail.com.
Alzheimer's Disease Genetics Consortium
Vanderbilt University Medical Center · USUniversity of Miami · USCase Western Reserve University · USUniversity of Pennsylvania · USBoston University · USColumbia University · USPennsylvania State University · USUniversity of Washington · USVanderbilt University · US
Funding
Alzheimer's Disease Neuroimaging Initiative - SupplementU01AG024904 · NIA · NORTHERN CALIFORNIA INSTITUTE RES &EDUC · PI WEINER, MICHAEL W · 2004 to 2015
$121.0MNational Centralized Repository for Alzheimer's Disease and Related Dementias (NCRAD)U24AG021886 · NIA · INDIANA UNIV-PURDUE UNIV AT INDIANAPOLIS · PI TATIANA M. FOROUD · 2002 to 2026
$119.8MTRIAL OF VALPROATE TO ATTENUATE THE PROGRESSION OF ADU01AG010483 · NIA · UNIVERSITY OF ROCHESTER · PI AISEN, PAUL S. · 1991 to 2012
$116.2MProject-005UL1TR001445 · NCATS · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · PI BREDELLA, MIRIAM ANTOINETTE, HOCHMAN, JUDITH S · 2015 to 2025
$103.5MNATIONAL ALZHEIMERS COORDINATING CENTER (NACC)U01AG016976 · NIA · UNIVERSITY OF WASHINGTON · PI KUKULL, WALTER ANTHONY · 1999 to 2020
$72.8MSmartphone-Based "Burst" Cognitive AssessmentsP01AG003991 · NIA · WASHINGTON UNIVERSITY · PI JOHN MORRIS · 1985 to 2026
$69.5MTDP-43 Loss-of-Function: Biology to BiomarkersP01AG019724 · NIA · UNIVERSITY OF PENNSYLVANIA · PI Jennifer Merrilees · 2002 to 2026
$67.2MAlzheimer's Disease Genetics ConsortiumU01AG032984 · NIA · UNIVERSITY OF PENNSYLVANIA · PI SCHELLENBERG, GERARD DAVID · 2009 to 2024
$60.4MTHERAPEUTIC EFFECTS OF INTRA-NASAL INSULIN DETEMIRP50AG005136 · NIA · UNIVERSITY OF WASHINGTON · PI GRABOWSKI, THOMAS J. · 1985 to 2019
$57.2MVIRUS-INDUCED BRAIN PATHOLOGYP50AG005131 · NIA · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI BREWER, JAMES B · 1985 to 2018
$55.4MWASHINGTON UNIVERSITY ALZHEIMERS DISEASE RESEARCH CENTERP50AG005681 · NIA · WASHINGTON UNIVERSITY · PI FAGAN, ANNE · 1985 to 2019
$52.1MSUPPLEMENT TO RUSH ALZHEIMERS DISEASE CENTER COREP30AG010161 · NIA · RUSH UNIVERSITY MEDICAL CENTER · PI LEURGANS, SUE E. · 1991 to 2020
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Abstract
Late-onset Alzheimer disease (AD) has a complex genetic etiology, involving locus heterogeneity, polygenic inheritance, and gene-gene interactions; however, the investigation of interactions in recent genome-wide association studies has been limited. We used a biological knowledge-driven approach to evaluate gene-gene interactions for consistency across 13 data sets from the Alzheimer Disease Genetics Consortium. Fifteen single nucleotide polymorphism (SNP)-SNP pairs within 3 gene-gene combinations were identified: SIRT1 × ABCB1, PSAP × PEBP4, and GRIN2B × ADRA1A. In addition, we extend a previously identified interaction from an endophenotype analysis between RYR3 × CACNA1C. Finally, post hoc gene expression analyses of the implicated SNPs further implicate SIRT1 and ABCB1, and implicate CDH23 which was most recently identified as an AD risk locus in an epigenetic analysis of AD. The observed interactions in this article highlight ways in which genotypic variation related to disease may depend on the genetic context in which it occurs. Further, our results highlight the utility of evaluating genetic interactions to explain additional variance in AD risk and identify novel molecular mechanisms of AD pathogenesis.
Indexed as
Datasets as TopicGenetic Association StudiesAlzheimer DiseaseATP Binding Cassette Transporter, Subfamily BCadherin Related ProteinsCadherinsCalcium Channels, L-TypeDisease ProgressionEpistasis, GeneticFemaleHumansMaleModels, GeneticPhosphatidylethanolamine Binding ProteinPolymorphism, Single NucleotideReceptors, Adrenergic, alpha-1ABCB1 protein, humanADRA1A protein, humanATP Binding Cassette Transporter, Subfamily BCACNA1C protein, humanCadherin Related ProteinsCadherinsCalcium Channels, L-TypeCDH23 protein, humanNR2B NMDA receptorPE-binding protein 4, humanPhosphatidylethanolamine Binding ProteinPSAP protein, humanReceptors, Adrenergic, alpha-1Receptors, N-Methyl-D-AspartateRyanodine Receptor Calcium Release ChannelSaposinsSIRT1 protein, humanSirtuin 1Alzheimer diseaseBiofilterEpistasisGene-gene interactions
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