ArticleAlzheimer's & dementia : the journal of the Alzheimer's Association2015
Linkage analyses in Caribbean Hispanic families identify novel loci associated with familial late-onset Alzheimer's disease.
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Article in Alzheimer's & dementia : the journal of the Alzheimer's Association, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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17 citing papers in PubMed, 26 citations in OpenAlex.
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- Interpretable AI for inference of causal molecular relationships from omics data.Science advances · 2025Article
- Whole-genome sequencing study in Koreans identifies novel loci for Alzheimer's disease.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2024Article
- Genetic analyses in multiplex families confirms chromosome 5q35 as a risk locus for Alzheimer's Disease in individuals of African Ancestry.Neurobiology of aging · 2024Article
- The Early-Onset Alzheimer's Disease Whole-Genome Sequencing Project: Study design and methodology.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2023Article
- A global view of the genetic basis of Alzheimer disease.Nature reviews. Neurology · 2023Review
- The National Institute on Aging Late-Onset Alzheimer's Disease Family Based Study: A resource for genetic discovery.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2022Article
- Including ethnic minorities in dementia research: Recommendations from a scoping review.Alzheimer's & dementia (New York, N. Y.) · 2022Article
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- The Puerto Rico Alzheimer Disease Initiative (PRADI): A Multisource Ascertainment Approach.Frontiers in genetics · 2019Article
- Analysis of pedigree data in populations with multiple ancestries: Strategies for dealing with admixture in Caribbean Hispanic families from the ADSP.Genetic epidemiology · 2018Article
- Differential α-synuclein expression contributes to selective vulnerability of hippocampal neuron subpopulations to fibril-induced toxicity.Acta neuropathologica · 2018Article
- Whole genome sequencing of Caribbean Hispanic families with late-onset Alzheimer's disease.Annals of clinical and translational neurology · 2018Article
- Linkage analysis of multiplex Caribbean Hispanic families loaded for unexplained early-onset cases identifies novel Alzheimer's disease loci.Alzheimer's & dementia (Amsterdam, Netherlands) · 2018Article
- The Alzheimer's Disease Sequencing Project: Study design and sample selection.Neurology. Genetics · 2017Article
- Genomic variants, genes, and pathways of Alzheimer's disease: An overview.American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics · 2017Review
- Genome-wide linkage analyses of non-Hispanic white families identify novel loci for familial late-onset Alzheimer's disease.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2016Article
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Authors and funding
16 authors at 11 institutions in 1 country.
Sandra BarralTaub Institute for Research on Alzheimer's Disease and the Aging Brain, Columbia University Medical Center, New York, NY, USA; Gertrude H. Sergievsky Center, Columbia University Medical Center, New York, NY, USA; Department of Neurology, Columbia University Medical Center and New York Presbyterian Hospital, New York, NY, USA.
Rong ChengTaub Institute for Research on Alzheimer's Disease and the Aging Brain, Columbia University Medical Center, New York, NY, USA; Gertrude H. Sergievsky Center, Columbia University Medical Center, New York, NY, USA.
Christiane ReitzTaub Institute for Research on Alzheimer's Disease and the Aging Brain, Columbia University Medical Center, New York, NY, USA; Gertrude H. Sergievsky Center, Columbia University Medical Center, New York, NY, USA; Department of Neurology, Columbia University Medical Center and New York Presbyterian Hospital, New York, NY, USA; Department of Epidemiology, School of Public Health, Columbia University, New York, NY, USA.
Badri VardarajanTaub Institute for Research on Alzheimer's Disease and the Aging Brain, Columbia University Medical Center, New York, NY, USA; Gertrude H. Sergievsky Center, Columbia University Medical Center, New York, NY, USA; Department of Neurology, Columbia University Medical Center and New York Presbyterian Hospital, New York, NY, USA.
Joseph LeeTaub Institute for Research on Alzheimer's Disease and the Aging Brain, Columbia University Medical Center, New York, NY, USA; Gertrude H. Sergievsky Center, Columbia University Medical Center, New York, NY, USA; Department of Epidemiology, School of Public Health, Columbia University, New York, NY, USA.
Brian KunkleThe John P. Hussman Institute for Human Genomics, University of Miami, Miami, FL, USA.
Gary BeechamThe John P. Hussman Institute for Human Genomics, University of Miami, Miami, FL, USA.
Laura S CantwellPerelman School of Medicine University of Pennsylvania, Philadelphia, PA, USA.
Margaret A Pericak-VanceThe John P. Hussman Institute for Human Genomics, University of Miami, Miami, FL, USA; Dr. John T. Macdonald Foundation Department of Human Genetics, Miller School of Medicine, University of Miami, Miami, FL, USA.
Lindsay A FarrerDepartment of Biostatistics, Boston University School of Public Health, Boston, MA, USA; Department of Medicine (Biomedical Genetics), Boston University School of Medicine and Public Health, Boston, MA, USA; Department of Neurology, Boston University School of Medicine and Public Health, Boston, MA, USA; Department of Ophthalmology, Boston University School of Medicine and Public Health, Boston, MA, USA; Department of Epidemiology, Boston University School of Medicine and Public Health, Boston, MA, USA.
Jonathan L HainesDepartment of Epidemiology & Biostatistics, Case Western Reserve University, Cleveland, OH, USA.
Alison M GoateDepartment of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Tatiana ForoudDepartment of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, IN, USA.
Eric BoerwinkleDepartment of Epidemiology, Human Genetics, and Environmental Sciences (EHGES), University of Texas School of Public Health at Houston, Houston, TX, USA; Human Genetics Center, School of Public Health, University of Texas Health Science Center at Houston, Houston, TX, USA.
Gerard D SchellenbergPerelman School of Medicine University of Pennsylvania, Philadelphia, PA, USA.
Richard MayeuxTaub Institute for Research on Alzheimer's Disease and the Aging Brain, Columbia University Medical Center, New York, NY, USA; Gertrude H. Sergievsky Center, Columbia University Medical Center, New York, NY, USA; Department of Neurology, Columbia University Medical Center and New York Presbyterian Hospital, New York, NY, USA; Department of Epidemiology, School of Public Health, Columbia University, New York, NY, USA. Electronic address: rpm2@cumc.columbia.edu.
Columbia University Irving Medical Center · USNewYork–Presbyterian Hospital · USUniversity of Miami · USUniversity of Pennsylvania · USBoston University · USCase Western Reserve University · USColumbia University · USDr. John T. Macdonald Foundation · USIcahn School of Medicine at Mount Sinai · USIndiana University School of MedicineThe University of Texas Health Science Center at Houston · US
Funding
National 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
$119.8MAlzheimer's Disease Genetics ConsortiumU01AG032984 · NIA · UNIVERSITY OF PENNSYLVANIA · PI SCHELLENBERG, GERARD DAVID · 2009 to 2024
$60.4MSatellite Diagnostic and Treatment Clinic CoreP50AG008702 · NIA · COLUMBIA UNIV NEW YORK MORNINGSIDE · PI DE JAGER, PHILIP L · 1989 to 2019
$46.3MThe 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
$31.4MNeuropathology CoreP30AG013846 · NIA · BOSTON UNIVERSITY MEDICAL CAMPUS · PI KOWALL, NEIL W. · 1996 to 2020
$29.1MQuality Assurance and Quality Control Project Management: Improving Submissions and Study Conduct in the Human Subjects Research Prior Approval ProcessUL1TR002529 · NCATS · INDIANA UNIVERSITY INDIANAPOLIS · PI MOE, SHARON M, WIEHE, SARAH ELIZABETH · 2018 to 2022
$27.2MIndiana Clinical and Translational Sciences InstituteUL1TR001108 · NCATS · INDIANA UNIVERSITY INDIANAPOLIS · PI DENNE, SCOTT C., SHEKHAR, ANANTHA · 2013 to 2017
$23.3MConsortium for Alzheimers Sequence Analysis (CASA)UF1AG047133 · NIA · UNIVERSITY OF PENNSYLVANIA · PI FARRER, LINDSAY A., HAINES, JONATHAN L · 2014 to 2014
$12.6MGenetic Epidemiology of Alzheimer's Disease in HispanicsR37AG015473 · NIA · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI MAYEUX, RICHARD P · 2004 to 2013
$10.8MEpidemiology of Biomarkers of Risk and Progression in LOADR01AG037212 · NIA · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI MAYEUX, RICHARD P, SCHUPF, NICOLE · 2010 to 2015
$10.1MGenetic Consortium for Late Onset Alzheimer's DiseaseU24AG026395 · NIA · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI MAYEUX, RICHARD P · 2005 to 2009
$10.1MGENETIC EPIDEMIOLOGY OF ALZHEIMERS DISEASE IN HISPANICSR01AG015473 · NIA · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI MAYEUX, RICHARD · 1999 to 2003
$4.6MNCATS NIH HHS UL1 TR001108NIA NIH HHS 5P50AG008702-25NIA NIH HHS K23 AG034550NIA NIH HHS K23AG034550NIA NIH HHS P30 AG013846NIA NIH HHS P30-AG13846NIA NIH HHS P50 AG008702NIA NIH HHS R01 AG015473NIA NIH HHS R01 AG025259NIA NIH HHS R01-AG025259NIA NIH HHS R01 AG037212NIA NIH HHS R01 AG041797NIA NIH HHS R37 AG015473NIA NIH HHS R37AG015473NIA NIH HHS RF1 AG015473NIA NIH HHS U01 AG032984NIA NIH HHS U24 AG021886NIA NIH HHS U24 AG026395NIA NIH HHS U24 AG056270NIA NIH HHS UF1 AG047133NIA NIH HHS UO1AG032984
Abstract
introductionWe performed linkage analyses in Caribbean Hispanic families with multiple late-onset Alzheimer's disease (LOAD) cases to identify regions that may contain disease causative variants.
methodsWe selected 67 LOAD families to perform genome-wide linkage scan. Analysis of the linked regions was repeated using the entire sample of 282 families. Validated chromosomal regions were analyzed using joint linkage and association.
resultsWe identified 26 regions linked to LOAD (HLOD ≥3.6). We validated 13 of the regions (HLOD ≥2.5) using the entire family sample. The strongest signal was at 11q12.3 (rs2232932: HLODmax = 4.7, Pjoint = 6.6 × 10(-6)), a locus located ∼2 Mb upstream of the membrane-spanning 4A gene cluster. We additionally identified a locus at 7p14.3 (rs10255835: HLODmax = 4.9, Pjoint = 1.2 × 10(-5)), a region harboring genes associated with the nervous system (GARS, GHRHR, and NEUROD6). DISCUSSION: Future sequencing efforts should focus on these regions because they may harbor familial LOAD causative mutations.
Indexed as
Genetic LinkagePolymorphism, Single NucleotideAgedAged, 80 and overAlzheimer DiseaseChromosome MappingDominican RepublicFemaleGenetic Predisposition to DiseaseGenome-Wide Association StudyHispanic or LatinoHumansMaleMiddle AgedNew York CityPuerto RicoCaribbean Hispanic familiesJoint linkage and associationLate-onset Alzheimer's diseaseLinkage analysis
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