Evidence map›Paper›PMID 26366463›Full record

ArticleJAMA neurology2015

Association of Long Runs of Homozygosity With Alzheimer Disease Among African American Individuals.

Mahdi Ghani, Christiane Reitz, Rong Cheng, Badri Narayan Vardarajan, Gyungah Jun, Christine Sato, Adam Naj, Ruchita Rajbhandary, Li-San Wang, Otto Valladares and 39 more

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

Article in JAMA neurology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.

0numbers the graph read from it
0cells of the map it votes in
31citing papers in PubMed
4.0field-weighted citation impact, top 6% of its field
1 · What the graph read from it

What it found

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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

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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

31 citing papers in PubMed, 51 citations in OpenAlex.

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  11. The impact of identity by descent on fitness and disease in dogs.Proceedings of the National Academy of Sciences of the United States of America · 2021
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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

49 authors at 20 institutions in 2 countries.

Mahdi GhaniTanz Centre for Research in Neurodegenerative Diseases, University of Toronto, Toronto, Ontario, Canada.
Christiane ReitzTaub Institute for Research on Alzheimer's Disease and the Aging Brain, College of Physicians and Surgeons, Columbia University, New York, New York3Gertrude H. Sergievsky Center, College of Physicians and Surgeons, Columbia University, New York, New York4.
Rong ChengTaub Institute for Research on Alzheimer's Disease and the Aging Brain, College of Physicians and Surgeons, Columbia University, New York, New York.
Badri Narayan VardarajanGertrude H. Sergievsky Center, College of Physicians and Surgeons, Columbia University, New York, New York.
Gyungah JunDepartment of Medicine (Biomedical Genetics), Boston University, Boston, Massachusetts6Department of Biostatistics, Boston University, Boston, Massachusetts7Department of Ophthalmology, Boston University, Boston, Massachusetts.
Christine SatoTanz Centre for Research in Neurodegenerative Diseases, University of Toronto, Toronto, Ontario, Canada.
Adam NajThe John P. Hussman Institute for Human Genomics, University of Miami, Miami, Florida.
Ruchita RajbhandaryThe John P. Hussman Institute for Human Genomics, University of Miami, Miami, Florida.
Li-San WangDepartment of Pathology and Laboratory Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia.
Otto ValladaresDepartment of Pathology and Laboratory Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia.
Chiao-Feng LinDepartment of Pathology and Laboratory Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia.
Eric B LarsonDepartment of Medicine, University of Washington, Seattle11Group Health Research Institute, Group Health, Seattle, Washington.
Neill R Graff-RadfordDepartment of Neuroscience, Mayo Clinic, Jacksonville, Florida13Department of Neurology, Mayo Clinic, Jacksonville, Florida.
Denis EvansRush Institute for Healthy Aging, Department of Internal Medicine, Rush University Medical Center, Chicago, Illinois.
Philip L De JagerProgram in Translational Neuropsychiatric Genomics, Department of Neurology, Brigham and Women's Hospital, Boston, Massachusetts16Harvard Medical School, Boston, Massachusetts17Program in Medical and Population Genetics, The Broad Institute, Cambridge, Ma.
Paul K CraneDepartment of Medicine, University of Washington, Seattle.
Joseph D BuxbaumDepartment of Psychiatry, Mount Sinai School of Medicine, New York, New York19Department of Genetics and Genomics Sciences, Mount Sinai School of Medicine, New York, New York20Department of Neuroscience, Mount Sinai School of Medicine, New York, New York2.
Jill R MurrellDepartment of Medical and Molecular Genetics, Indiana University, Indianapolis.
Towfique RajHarvard Medical School, Boston, Massachusetts.
Nilufer Ertekin-TanerDepartment of Neuroscience, Mayo Clinic, Jacksonville, Florida13Department of Neurology, Mayo Clinic, Jacksonville, Florida.
Mark LogueDepartment of Medicine (Biomedical Genetics), Boston University, Boston, Massachusetts.
Clinton T BaldwinDepartment of Medicine (Biomedical Genetics), Boston University, Boston, Massachusetts.
Robert C GreenHarvard Medical School, Boston, Massachusetts23Division of Genetics, Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts24Partners Center for Personalized Genetic Medicine, Brigham and Women's Hospital, Boston, Massachusetts.
Lisa L BarnesDepartment of Neurological Sciences, Rush University Medical Center, Chicago, Illinois26Department of Behavioral Sciences, Rush University Medical Center, Chicago, Illinois.
Laura B CantwellDepartment of Pathology and Laboratory Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia.
M Daniele FallinDepartment of Epidemiology, Johns Hopkins University School of Public Health, Baltimore, Maryland.
Rodney C P GoSchool of Public Health, University of Alabama at Birmingham.
Patrick A GriffithSABA University School of Medicine, SABA, Dutch Caribbean.
Thomas O ObisesanDivision of Geriatrics, Howard University Hospital, Washington, DC.
Jennifer J ManlyTaub Institute for Research on Alzheimer's Disease and the Aging Brain, College of Physicians and Surgeons, Columbia University, New York, New York4Department of Neurology, College of Physicians and Surgeons, Columbia University, New York, New York.
Kathryn L LunettaDepartment of Biostatistics, Boston University, Boston, Massachusetts.
M Ilyas KambohDepartment of Human Genetics, University of Pittsburgh, Pittsburgh, Pennsylvania32Alzheimer's Disease Research Center, University of Pittsburgh, Pittsburgh, Pennsylvania.
Oscar L LopezAlzheimer's Disease Research Center, University of Pittsburgh, Pittsburgh, Pennsylvania.
David A BennettDepartment of Neurological Sciences, Rush University Medical Center, Chicago, Illinois33Rush Alzheimer's Disease Center, Rush University Medical Center, Chicago, Illinois.
Hugh HendrieIndiana University Center for Aging Research, Indianapolis35Department of Psychiatry, Indiana University School of Medicine, Indianapolis36Regenstrief Institute Inc, Indianapolis, Indiana.
Kathleen S HallDepartment of Psychiatry, Indiana University School of Medicine, Indianapolis.
Alison M GoateHope Center Program on Protein Aggregation and Neurodegeneration, Department of Psychiatry, Washington University School of Medicine, St Louis, Missouri.
Goldie S ByrdDepartment of Biology, North Carolina A & T University, Greensboro.
Walter A KukullNational Alzheimer's Coordinating Center, Department of Epidemiology, University of Washington, Seattle.
Tatiana M ForoudDepartment of Behavioral Sciences, Rush University Medical Center, Chicago, Illinois.
Jonathan L HainesVanderbilt Center for Human Genetics Research, Department of Molecular Physiology and Biophysics, Vanderbilt University, Nashville, Tennessee.
Lindsay A FarrerDepartment of Medicine (Biomedical Genetics), Boston University, Boston, Massachusetts6Department of Biostatistics, Boston University, Boston, Massachusetts7Department of Ophthalmology, Boston University, Boston, Massachusetts41Department of Neurology, Bo.
Margaret A Pericak-VanceThe John P. Hussman Institute for Human Genomics, University of Miami, Miami, Florida.
Joseph H LeeTaub Institute for Research on Alzheimer's Disease and the Aging Brain, College of Physicians and Surgeons, Columbia University, New York, New York3Gertrude H. Sergievsky Center, College of Physicians and Surgeons, Columbia University, New York, New York4.
Gerard D SchellenbergDepartment of Pathology and Laboratory Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia.
Peter St George-HyslopTanz Centre for Research in Neurodegenerative Diseases, University of Toronto, Toronto, Ontario, Canada.
Richard MayeuxTaub Institute for Research on Alzheimer's Disease and the Aging Brain, College of Physicians and Surgeons, Columbia University, New York, New York3Gertrude H. Sergievsky Center, College of Physicians and Surgeons, Columbia University, New York, New York4.
Ekaterina RogaevaTanz Centre for Research in Neurodegenerative Diseases, University of Toronto, Toronto, Ontario, Canada.
Alzheimer’s Disease Genetics Consortium
Boston University · USColumbia University · USOccupational Cancer Research Centre · CARush University Medical Center · USIndiana University – Purdue University Indianapolis · USPhiladelphia University · USUniversity of Miami · USUniversity of Pittsburgh · USHarvard University · USUniversity of Pennsylvania · USUniversity of Washington · USBrigham and Women's Hospital · USHoward University Hospital · USIcahn School of Medicine at Mount Sinai · USJacksonville College · USJohns Hopkins University · USNorth Carolina Agricultural and Technical State University · USSeattle University · USUniversity of Alabama at Birmingham · USVanderbilt University · 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
$119.8M
TRIAL OF VALPROATE TO ATTENUATE THE PROGRESSION OF ADU01AG010483 · NIA · UNIVERSITY OF ROCHESTER · PI AISEN, PAUL S. · 1991 to 2012
$116.2M
NATIONAL ALZHEIMERS COORDINATING CENTER (NACC)U01AG016976 · NIA · UNIVERSITY OF WASHINGTON · PI KUKULL, WALTER ANTHONY · 1999 to 2020
$72.8M
Smartphone-Based "Burst" Cognitive AssessmentsP01AG003991 · NIA · WASHINGTON UNIVERSITY · PI Tammie Lee Smith Benzinger · 1985 to 2026
$69.5M
TDP-43 Loss-of-Function: Biology to BiomarkersP01AG019724 · NIA · UNIVERSITY OF PENNSYLVANIA · PI Jennifer Merrilees · 2002 to 2026
$67.2M
Alzheimer's Disease Genetics ConsortiumU01AG032984 · NIA · UNIVERSITY OF PENNSYLVANIA · PI SCHELLENBERG, GERARD DAVID · 2009 to 2024
$60.4M
THERAPEUTIC EFFECTS OF INTRA-NASAL INSULIN DETEMIRP50AG005136 · NIA · UNIVERSITY OF WASHINGTON · PI JAYADEY, SUMAN · 1985 to 2019
$57.2M
VIRUS-INDUCED BRAIN PATHOLOGYP50AG005131 · NIA · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI BREWER, JAMES B · 1985 to 2018
$55.4M
WASHINGTON UNIVERSITY ALZHEIMERS DISEASE RESEARCH CENTERP50AG005681 · NIA · WASHINGTON UNIVERSITY · PI MORRIS, JOHN · 1985 to 2019
$52.1M
The natural history of AB accumulation in preclinical ADP01AG026276 · NIA · WASHINGTON UNIVERSITY · PI SCHINDLER, SUZANNE ELIZABETH · 2005 to 2025
$49.5M
SUPPLEMENT TO RUSH ALZHEIMERS DISEASE CENTER COREP30AG010161 · NIA · RUSH UNIVERSITY MEDICAL CENTER · PI BENNETT, DAVID ALAN · 1991 to 2020
$49.1M
Satellite Diagnostic and Treatment Clinic CoreP50AG008702 · NIA · COLUMBIA UNIV NEW YORK MORNINGSIDE · PI DE JAGER, PHILIP L · 1989 to 2019
$46.3M
CIHRMedical Research Council MC_G1000734NCATS NIH HHS UL1 TR001108NCI NIH HHS R01 CA129769NCI NIH HHS R01CA129769NCI NIH HHS U54 CA132378NCI NIH HHS U54 CA137788NCRR NIH HHS M01 RR000096NCRR NIH HHS MO1RR00096NCRR NIH HHS UL1RR02777NCRR NIH HHS UL1 RR029893NCRR NIH HHS UL1RR029893NHGRI NIH HHS U01 HG004610NHGRI NIH HHS U01 HG008657NHGRI NIH HHS UO1 HG004610NIA NIH HHS 5R01AG20688NIA NIH HHS AG005138NIA NIH HHS AG010491NIA NIH HHS AG019757NIA NIH HHS AG021547NIA NIH HHS AG025688NIA NIH HHS AG027944NIA NIH HHS AG030653NIA NIH HHS AG05128NIA NIH HHS K23 AG034550NIA NIH HHS K23AG034550NIA NIH HHS P01 AG002219NIA NIH HHS P01AG002219NIA NIH HHS P01 AG003991NIA NIH HHS P01 AG007232NIA NIH HHS P01 AG010491NIA NIH HHS P01 AG019724NIA NIH HHS P01 AG026276NIA NIH HHS P01AG026276NIA NIH HHS P01 AG03991NIA NIH HHS P01-AG07232NIA NIH HHS P30 AG008017NIA NIH HHS P30AG008017NIA NIH HHS P30 AG008051NIA NIH HHS P30 AG010124NIA NIH HHS P30AG010124NIA NIH HHS P30 AG010129NIA NIH HHS P30AG010129NIA NIH HHS P30 AG010133NIA NIH HHS P30 AG010161NIA NIH HHS P30 AG012300NIA NIH HHS P30AG012300NIA NIH HHS P30 AG013846NIA NIH HHS P30 AG013854NIA NIH HHS P30AG013854NIA NIH HHS P30 AG019610NIA NIH HHS P30AG019610NIA NIH HHS P30 AG028377NIA NIH HHS P30AG028377NIA NIH HHS P30 AG028383NIA NIH HHS P30AG028383NIA NIH HHS P30AG08051NIA NIH HHS P30AG10133NIA NIH HHS P30AG10161NIA NIH HHS P30-AG13846NIA NIH HHS P30AG13846NIA NIH HHS P50 AG005128NIA NIH HHS P50 AG005131NIA NIH HHS P50AG005131NIA NIH HHS P50 AG005133NIA NIH HHS P50 AG005134NIA NIH HHS P50AG005134NIA NIH HHS P50 AG005136NIA NIH HHS P50AG005136NIA NIH HHS P50 AG005138NIA NIH HHS P50 AG005142NIA NIH HHS P50AG005142NIA NIH HHS P50 AG005146NIA NIH HHS P50AG005146NIA NIH HHS P50 AG005681NIA NIH HHS P50 AG008671NIA NIH HHS P50AG008671NIA NIH HHS P50 AG008702NIA NIH HHS P50AG008702NIA NIH HHS P50 AG016570NIA NIH HHS P50AG016570NIA NIH HHS P50 AG016573NIA NIH HHS P50AG016573NIA NIH HHS P50 AG016574NIA NIH HHS P50AG016575NIA NIH HHS P50AG016576NIA NIH HHS P50AG016577NIA NIH HHS P50 AG016582NIA NIH HHS P50AG016582NIA NIH HHS P50AG019724NIA NIH HHS P50 AG023501NIA NIH HHS P50AG023501NIA NIH HHS P50 AG025688NIA NIH HHS P50 AG05681NIA NIH HHS P50AG16574NIA NIH HHS R01 AG009029NIA NIH HHS R01 AG009956NIA NIH HHS R01AG009956NIA NIH HHS R01 AG011101NIA NIH HHS R01 AG015473NIA NIH HHS R01 AG015819NIA NIH HHS R01 AG017173NIA NIH HHS R01AG017173NIA NIH HHS R01 AG017917NIA NIH HHS R01 AG018732NIA NIH HHS R01 AG019085NIA NIH HHS R01AG019085NIA NIH HHS R01 AG019757NIA NIH HHS R01 AG020688NIA NIH HHS R01 AG021547NIA NIH HHS R01 AG022018NIA NIH HHS R01 AG025259NIA NIH HHS R01AG025259NIA NIH HHS R01 AG026390NIA NIH HHS R01 AG026916NIA NIH HHS R01AG026916NIA NIH HHS R01 AG027944NIA NIH HHS R01 AG028786NIA NIH HHS R01AG028786NIA NIH HHS R01 AG030146NIA NIH HHS R01 AG030653NIA NIH HHS R01 AG031581NIA NIH HHS R01AG031581NIA NIH HHS R01 AG032990NIA NIH HHS R01 AG033193NIA NIH HHS R01 AG037212NIA NIH HHS R01AG037212NIA NIH HHS R01 AG048927NIA NIH HHS R01 AG11101NIA NIH HHS R01AG15819NIA NIH HHS R01AG17917NIA NIH HHS R01AG22018NIA NIH HHS R01-AG25259NIA NIH HHS R01AG28786-01A1NIA NIH HHS R01AG30146NIA NIH HHS R01AG33193NIA NIH HHS R01-AG AG048927NIA NIH HHS R37 AG015473NIA NIH HHS RC2 AG036528NIA NIH HHS RC2-AG036528NIA NIH HHS RC2 AG036650NIA NIH HHS RF1 AG015473NIA NIH HHS RF1 AG015819NIA NIH HHS U01 AG006781NIA NIH HHS U01 AG010483NIA NIH HHS U01 AG016976NIA NIH HHS U01-AG016976NIA NIH HHS U01 AG032984NIA NIH HHS U01-AG032984NIA NIH HHS U01 AG046139NIA NIH HHS U01-AG10483NIA NIH HHS U24 AG021886NIA NIH HHS U24-AG021886NIA NIH HHS U24 AG026390NIA NIH HHS U24 AG026395NIA NIH HHS U24 AG041689NIA NIH HHS U24AG041689NIA NIH HHS UO1 AG032984NIA NIH HHS UO1 AG06781NIMHD NIH HHS P20 MD000546NIMH NIH HHS MH60451NIMH NIH HHS P50 MH060451NIMH NIH HHS R01 MH080295NIMH NIH HHS R01MH080295NINDS NIH HHS NS39764NINDS NIH HHS P50 NS039764NINDS NIH HHS R01 NS080820Wellcome Trust 081864Wellcome Trust 089703
6 · The paper itself

Abstract

importanceMutations in known causal Alzheimer disease (AD) genes account for only 1% to 3% of patients and almost all are dominantly inherited. Recessive inheritance of complex phenotypes can be linked to long (>1-megabase [Mb]) runs of homozygosity (ROHs) detectable by single-nucleotide polymorphism (SNP) arrays.

objectiveTo evaluate the association between ROHs and AD in an African American population known to have a risk for AD up to 3 times higher than white individuals. DESIGN, SETTING, AND

participantsCase-control study of a large African American data set previously genotyped on different genome-wide SNP arrays conducted from December 2013 to January 2015. Global and locus-based ROH measurements were analyzed using raw or imputed genotype data. We studied the raw genotypes from 2 case-control subsets grouped based on SNP array: Alzheimer's Disease Genetics Consortium data set (871 cases and 1620 control individuals) and Chicago Health and Aging Project-Indianapolis Ibadan Dementia Study data set (279 cases and 1367 control individuals). We then examined the entire data set using imputed genotypes from 1917 cases and 3858 control individuals. MAIN OUTCOMES AND MEASURES: The ROHs larger than 1 Mb, 2 Mb, or 3 Mb were investigated separately for global burden evaluation, consensus regions, and gene-based analyses.

resultsThe African American cohort had a low degree of inbreeding (F ~ 0.006). In the Alzheimer's Disease Genetics Consortium data set, we detected a significantly higher proportion of cases with ROHs greater than 2 Mb (P = .004) or greater than 3 Mb (P = .02), as well as a significant 114-kilobase consensus region on chr4q31.3 (empirical P value 2 = .04; ROHs >2 Mb). In the Chicago Health and Aging Project-Indianapolis Ibadan Dementia Study data set, we identified a significant 202-kilobase consensus region on Chr15q24.1 (empirical P value 2 = .02; ROHs >1 Mb) and a cluster of 13 significant genes on Chr3p21.31 (empirical P value 2 = .03; ROHs >3 Mb). A total of 43 of 49 nominally significant genes common for both data sets also mapped to Chr3p21.31. Analyses of imputed SNP data from the entire data set confirmed the association of AD with global ROH measurements (12.38 ROHs >1 Mb in cases vs 12.11 in controls; 2.986 Mb average size of ROHs >2 Mb in cases vs 2.889 Mb in controls; and 22% of cases with ROHs >3 Mb vs 19% of controls) and a gene-cluster on Chr3p21.31 (empirical P value 2 = .006-.04; ROHs >3 Mb). Also, we detected a significant association between AD and CLDN17 (empirical P value 2 = .01; ROHs >1 Mb), encoding a protein from the Claudin family, members of which were previously suggested as AD biomarkers. CONCLUSIONS AND RELEVANCE: To our knowledge, we discovered the first evidence of increased burden of ROHs among patients with AD from an outbred African American population, which could reflect either the cumulative effect of multiple ROHs to AD or the contribution of specific loci harboring recessive mutations and risk haplotypes in a subset of patients. Sequencing is required to uncover AD variants in these individuals.

Indexed as

HomozygoteAgedAlzheimer DiseaseBlack or African AmericanCase-Control StudiesChicagoGenes, RecessiveGenome-Wide Association StudyHumansIndianaPolymorphism, Single Nucleotide

Identifiers

PMID26366463
PMCPMC4641052
OpenAlexW1619053513

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