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Record W2586698568 · doi:10.1016/j.jalz.2016.12.012

Transethnic genome‐wide scan identifies novel Alzheimer's disease loci

2017· article· en· W2586698568 on OpenAlexaff
Gyungah Jun, Jaeyoon Chung, Jesse Mez, Robert C. Barber, Gary W. Beecham, David A. Bennett, Joseph D. Buxbaum, Goldie S. Byrd, Minerva M. Carrasquillo, Paul K. Crane, Carlos Cruchaga, Philip L. De Jager, Nilüfer Ertekin‐Taner, Denis A. Evans, M. Danielle Fallin, Tatiana Foroud, Robert P. Friedland, Alison Goate, Neill R. Graff‐Radford, Hugh C. Hendrie, Kathleen Hall, Kara L. Hamilton‐Nelson, Rivka Inzelberg, M. Ilyas Kamboh, John S. K. Kauwe, Walter A. Kukull, Brian W. Kunkle, Ryozo Kuwano, Eric B. Larson, Mark W. Logue, Jennifer J. Manly, Eden R. Martin, Thomas J. Montine, Shubhabrata Mukherjee, Adam C. Naj, Eric M. Reiman, Christiane Reitz, Richard Sherva, Peter St George‐Hyslop, Timothy Thornton, Steven G. Younkin, Badri N. Vardarajan, Li‐San Wang, Jens R. Wendlund, Ashley R. Winslow, Perrie M. Adams, Marilyn S. Albert, Roger L. Albin, Liana G. Apostolova, Steven E. Arnold, Sanjay Asthana, Craig Atwood, Michjael M Barmada, Lisa L. Barnes, Thomas G. Beach, James T. Becker, Eileen H. Bigio, Thomas D. Bird, Deborah Blacker, Bradley F. Boeve, James D. Bowen, Adam Boxer, James R. Burke, Nigel J. Cairns, Chuanhai Cao, Chris Carlson, Cynthia M. Carlsson, Regina M. Carney, Steven L. Carroll, Helena C. Chui, David G. Clark, Jason J. Corneveaux, David H. Cribbs, Elizabeth Crocco, Charles DeCarli, Steven T. DeKosky, F. Yesim Demirci, Malcolm Dick, Dennis W. Dickson, Rachelle S. Doody, Ranjan Duara, Kelley Faber, Thomas Fairchild, Kenneth B. Fallon, Martin R. Farlow, Steven H. Ferris, Matthew P. Frosch, Douglas Galasko, Marla Gearing, Daniel H. Geschwind, Bernardino Ghetti, John R. Gilbert, Jonathan D. Glass, Robert C. Green, John H. Growdon, Håkon Håkonarson, Ronald L. Hamilton, John Hardy, Lindy E. Harrell, Elizabeth Head, Lawrence S. Honig, Ryan Huebinger, Matthew J. Huentelman, Christine M. Hulette, Bradley T. Hyman, Gail P. Jarvik, Gregory A. Jicha, Lee‐Way Jin, Anna Karydas, Jeffrey Kaye, Ronald Kim, Edward H. Koo, Neil W. Kowall, Joel H. Kramer, Frank M. LaFerla, James J. Lah, James B. Leverenz, Allan I. Levey, Li Ge, Andrew P. Lieberman, Chiao‐Feng Lin, Oscar L. López, Constantine G. Lyketsos, Wendy J. Mack, Daniel Marson, Frank Martiniuk, Deborah C. Mash, Eliezer Masliah, Wayne C. McCormick, Susan M. McCurry, Andrew McDavid, Ann C. McKee, Marsel Mesulam, Bruce L. Miller, Carol A. Miller, Joshua W. Miller, John C. Morris, Jill R. Murrell, Amanda Myers, Sid E. O’Bryant, John Olichney, V. Shane Pankratz, Joseph E. Parisi, Amanda Partch, Henry L. Paulson, William Perry, Elaine R. Peskind, Ronald Petersen, Aimee Pierce, Wayne W. Poon, Huntington Potter, Joseph F. Quinn, Ashok Raj, Murray A. Raskind, ‌Barry Reisberg, Joan Reisch, John M. Ringman, Erik D. Roberson, Ekaterina Rogaeva, Howard J. Rosen, Roger N. Rosenberg, Donald R. Royall, Mark A. Sager, Mary Sano, Andrew J. Saykin, Julie A. Schneider, Lon S. Schneider, William W. Seeley, Amanda Smith, Joshua A. Sonnen, Salvatore Spina, Robert A. Stern, Rudolph E. Tanzi, Tricia A. Thornton‐Wells, John Q. Trojanowski, Juan C. Troncoso, Debby W. Tsuang, Vivianna M. Van Deerlin, Linda J. Van Eldik, Harry V. Vinters, Jean Paul Vonsattel, Sandra Weıntraub, Kathleen A. Welsh‐Bohmer, Jennifer Williamson, Sarah Wishnek, Randall L. Woltjer, Clinton B. Wright, Chuang‐Kuo Wu, Chang‐En Yu, Lei Yu, Xiaoling Zhang, Jonathan L. Haines, Richard Mayeux, Margaret A. Pericak‐Vance, Gerard Schellenberg, Kathryn L. Lunetta, Lindsay A. Farrer

Bibliographic record

VenueAlzheimer s & Dementia · 2017
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicGenetic Associations and Epidemiology
Canadian institutionsOccupational Cancer Research CentreUniversity of Toronto
FundersNational Center for Research ResourcesNational Institute of General Medical SciencesNational Cancer InstituteNational Human Genome Research InstituteNational Institute on AgingNational Center for Advancing Translational SciencesMedical Research CouncilUniversity of California, IrvineUniversity of California, San DiegoUniversity of California, DavisUniversity of California, Los AngelesNational Institutes of HealthRosetrees TrustBanner Alzheimer’s FoundationNational Institute of Neurological Disorders and StrokeUniversity of PittsburghJohns Hopkins UniversityUniversity of WashingtonBoston UniversityUniversity of MiamiNorthwestern UniversityNew York UniversityUniversity of KentuckyEmory UniversityUniversity of California, San FranciscoIndiana UniversityUniversity of PennsylvaniaVanderbilt UniversityMayo ClinicUniversity of MichiganUniversity of Southern CaliforniaWellcome TrustDuke UniversityColumbia UniversityRush UniversityNational Institute of Mental HealthNational Association for Colitis and Crohn's DiseaseUniversity of Alabama at BirminghamMassachusetts General HospitalGlaxoSmithKlineParkinson's UKUniversity of Arizona
KeywordsGenome-wide association studySingle-nucleotide polymorphismSNPGeneticsLocus (genetics)Genetic associationBiologyGenetic architectureAlleleApolipoprotein EDiseaseAlzheimer's diseaseGeneGenotypeMedicineQuantitative trait locusPathology

Abstract

fetched live from OpenAlex

Abstract Introduction Genetic loci for Alzheimer's disease (AD) have been identified in whites of European ancestry, but the genetic architecture of AD among other populations is less understood. Methods We conducted a transethnic genome‐wide association study (GWAS) for late‐onset AD in Stage 1 sample including whites of European Ancestry, African‐Americans, Japanese, and Israeli‐Arabs assembled by the Alzheimer's Disease Genetics Consortium. Suggestive results from Stage 1 from novel loci were followed up using summarized results in the International Genomics Alzheimer's Project GWAS dataset. Results Genome‐wide significant (GWS) associations in single‐nucleotide polymorphism (SNP)–based tests ( P < 5 × 10 −8 ) were identified for SNPs in PFDN1/HBEGF , USP6NL/ECHDC3 , and BZRAP1‐AS1 and for the interaction of the (apolipoprotein E) APOE ε4 allele with NFIC SNP. We also obtained GWS evidence ( P < 2.7 × 10 −6 ) for gene‐based association in the total sample with a novel locus, TPBG ( P = 1.8 × 10 −6 ). Discussion Our findings highlight the value of transethnic studies for identifying novel AD susceptibility loci.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame machine prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.

metaresearch head score (Codex)0.001
metaresearch head score (Gemma)0.001
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Observational · Consensus signal: Observational
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.004
Threshold uncertainty score0.008

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0010.001
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.001
Bibliometrics0.0010.001
Science and technology studies0.0010.000
Scholarly communication0.0010.000
Open science0.0000.001
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0020.000

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.033
GPT teacher head0.292
Teacher spread0.259 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designObservational
Domainnot available
GenreEmpirical

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

Quick stats

Citations210
Published2017
Admission routes1
Has abstractyes

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