Accès ouvert déclaré 2023 preprint

Multi-ancestry genome-wide meta-analysis of 56,241 individuals identifies LRRC4C, LHX5-AS1 and nominates ancestry-specific loci PTPRK , GRB14 , and KIAA0825 as novel risk loci for Alzheimer’s disease: the Alzheimer’s Disease Genetics Consortium

Farid Rajabli, Penelope Benchek, Giuseppe Tosto, Nicholas A. Kushch, Jin Sha, Katrina Bazemore, Congcong Zhu, Wan‐Ping Lee, Jacob Haut, Kara L. Hamilton‐Nelson, Nicholas R. Wheeler, Yi Zhao, John J. Farrell, Michelle Grunin, Yuk Yee Leung, Pavel P. Kuksa, Donghe Li, Eder Lúcio da Fonseca, Jesse Mez, Ellen L. Palmer, Jagan A. Pillai, Richard Sherva, Yeunjoo E. Song, Xiaoling Zhang, Taha Iqbal, Omkar Pathak, Otto Valladares, Amanda Kuzma, Erin L. Abner, Perrie M. Adams, Alyssa Aguirre, Marilyn S. Albert, Roger L. Albin, Mariet Allen, Lisa Alvarez, Liana G. Apostolova, Steven E. Arnold, Sanjay Asthana, Craig Atwood, Gayle Ayres, Clinton T. Baldwin, Robert C. Barber, Lisa L. Barnes, Sandra Barral, Thomas G. Beach, James T. Becker, Gary W. Beecham, Duane Beekly, Bruno A. Benítez, David A. Bennett, John Bertelson, Thomas D. Bird, Deborah Blacker, Bradley F. Boeve, James D. Bowen, Adam Boxer, James B. Brewer, James R. Burke, Jeffrey M. Burns, Joseph D. Buxbaum, Nigel J. Cairns, Laura B. Cantwell, Chuanhai Cao, Christopher S. Carlson, Cynthia M. Carlsson, Regina M. Carney, Minerva M. Carrasquillo, Scott Chasse, Marie‐Françoise Chesselet, Nathaniel A. Chin, Helena C. Chui, Jaeyoon Chung, Suzanne Craft, Paul K. Crane, David H. Cribbs, Elizabeth Crocco, Carlos Cruchaga, Michael L. Cuccaro, C. Munro Cullum, Eveleen Darby, Bárbara Davis, Philip L. De Jager, Charles DeCarli, John C. DeToledo, Malcolm Dick, Dennis W. Dickson, Beth A. Dombroski, Rachelle S. Doody, Ranjan Duara, NIlüfer Ertekin-Taner, Denis A. Evans, Kelley M. Faber, Thomas Fairchild, Kenneth B. Fallon, David W. Fardo, Martin R. Farlow, Victoria Fernandez-Hernandez, Steven H. Ferris, Tatiana M. Foroud, Matthew P. Frosch, Brian Fulton‐Howard, Douglas Galasko, Adriana C. Gamboa, Marla Gearing, Daniel H. Geschwind, Bernardino Ghetti, John R. Gilbert, Alison Goate, Thomas J. Grabowski, Neill R. Graff‐Radford, Robert C. Green, John H. Growdon, Håkon Håkonarson, James Hall, Ronald L. Hamilton, Oscar Harari, John Hardy, Lindy E. Harrell, Elizabeth Head, Victor W. Henderson, Michelle L. Hernandez, Timothy J. Hohman, Lawrence S. Honig, Ryan M. Huebinger, Matthew J. Huentelman, Christine M. Hulette, Bradley T. Hyman, Linda S. Hynan, Laura Ibáñez, Gail P. Jarvik, Suman Jayadev, Lee‐Way Jin, Kim G. Johnson, Leigh Johnson, M. Ilyas Kamboh, Anna M. Karydas, Mindy J. Katz, John S. K. Kauwe, C. Dirk Keene, Aisha Khaleeq, Ronald Kim, Janice Knebl, Neil W. Kowall, Joel H. Kramer, Walter A. Kukull, Frank M. LaFerla, James J. Lah, Eric B. Larson, Alan J. Lerner, James B. Leverenz, Allan I. Levey, Andrew P. Lieberman, Richard B. Lipton, Mark W. Logue, Oscar L. López, Kathryn L. Lunetta, Constantine G. Lyketsos, Douglas Mains, Margaret E. Flanagan, Daniel Marson, Eden R. Martin, Frank Martiniuk, Deborah C. Mash, Eliezer Masliah, Paul J. Massman, Arjun V. Masurkar, Wayne C. McCormick, Susan M. McCurry, Andrew McDavid, Stefan McDonough, Ann C. McKee, Marsel Mesulam, Bruce L. Miller, Carol A. Miller, Joshua W. Miller, Thomas J. Montine, Edwin S. Monuki, John C. Morris, Shubhabrata Mukherjee, Amanda Myers, Trung Dung Nguyen, Sid E. O’Bryant, John Olichney, Marcia G. Ory, Raymond F. Palmer, Joseph E. Parisi, Henry L. Paulson, Valory Pavlik, David Paydarfar, Victòria Aurora Ferrer Pérez, Elaine R. Peskind, Ronald Petersen, Aimee Pierce, Marsha J. Polk, Wayne W. Poon, Huntington Potter, Liming Qu, Mary Quiceno, Joseph F. Quinn, Ashok Raj, Murray A. Raskind, Eric M. Reiman, ‌Barry Reisberg, Joan Reisch, John M. Ringman, Erik D. Roberson, Monica Rodriguear, 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, Susan H. Slifer, Scott A. Small, Amanda Smith, Janet P. Smith, Joshua A. Sonnen, Salvatore Spina, Peter St George‐Hyslop, Robert A. Stern, Alan Stevens, Stephen M. Strittmatter, David L. Sultzer, Russell H. Swerdlow, Rudolph E. Tanzi, Jeffrey L. Tilson, John Q. Trojanowski, Juan C. Troncoso, Debby W. Tsuang, Vivianna M. Van Deerlin, Linda J. Van Eldik, Jeffery M. Vance, Badri N. Vardarajan, Robert Vassar, Harry V. Vinters, Jean‐Paul Vonsattel, Sandra Weıntraub, Kathleen A. Welsh‐Bohmer, Patrice L. Whitehead, Ellen M. Wijsman, Kirk C. Wilhelmsen, Benjamin Williams, Jennifer Williamson, Henrik Wilms, Thomas S. Wingo, Thomas Wısnıewskı, Randall L. Woltjer, Martin Woon, Clinton B. Wright, Chuang‐Kuo Wu, Steven G. Younkin, Chang‐En Yu, Lei Yu, Xiongwei Zhu, Brian W. Kunkle, William S. Bush, Li‐San Wang, Lindsay A. Farrer, Jonathan L. Haines, Richard Mayeux, Margaret A. Pericak‐Vance, Gerard D. Schellenberg, Gyungah Jun, Christiane Reitz, Adam C. Naj

11Citations signalées, ce qui n’est pas une note de qualité

93Institutions déclarées

3Pays d’affiliation déclarés

Rattachement africain : us, gb, ca. Niveau de preuve : code pays fourni par la source.

Le résumé fourni par la source

ABSTRACT Limited ancestral diversity has impaired our ability to detect risk variants more prevalent in non-European ancestry groups in genome-wide association studies (GWAS). We constructed and analyzed a multi-ancestry GWAS dataset in the Alzheimer’s Disease (AD) Genetics Consortium (ADGC) to test for novel shared and ancestry-specific AD susceptibility loci and evaluate underlying genetic architecture in 37,382 non-Hispanic White (NHW), 6,728 African American, 8,899 Hispanic (HIS), and 3,232 East Asian individuals, performing within-ancestry fixed-effects meta-analysis followed by a cross-ancestry random-effects meta-analysis. We identified 13 loci with cross-ancestry associations including known loci at/near CR1 , BIN1 , TREM2 , CD2AP , PTK2B , CLU , SHARPIN , MS4A6A , PICALM , ABCA7 , APOE and two novel loci not previously reported at 11p12 ( LRRC4C ) and 12q24.13 ( LHX5-AS1 ). Reflecting the power of diverse ancestry in GWAS, we observed the SHARPIN locus using 7.1% the sample size of the original discovering single-ancestry GWAS (n=788,989). We additionally identified three GWS ancestry-specific loci at/near ( PTPRK ( P =2.4×10 -8 ) and GRB14 ( P =1.7×10 -8 ) in HIS), and KIAA0825 ( P =2.9×10 -8 in NHW). Pathway analysis implicated multiple amyloid regulation pathways (strongest with P adjusted =1.6×10 -4 ) and the classical complement pathway ( P adjusted =1.3×10 -3 ). Genes at/near our novel loci have known roles in neuronal development ( LRRC4C, LHX5-AS1 , and PTPRK ) and insulin receptor activity regulation ( GRB14 ). These findings provide compelling support for using traditionally-underrepresented populations for gene discovery, even with smaller sample sizes.

Ce résumé expose les affirmations des auteurs. BNTIC ne l’interprète pas comme une validation indépendante des résultats.

Le contrôle bibliographique ouvert

DOI retrouvé dans Crossref DOI retrouvé, mais le titre doit être comparé manuellement.

Titre Crossref: Multi-ancestry genome-wide meta-analysis of 56,241 individuals identifies LRRC4C, LHX5-AS1 and nominates ancestry-specific loci PTPRK , GRB14 , and KIAA0825 as novel risk loci for Alzheimer’s disease: the Alzheimer’s Disease Genetics Consortium
Date Crossref: 08/07/2023
Éditeur: openRxiv
Type: posted-content

Ce recoupement confirme des métadonnées liées au DOI. Il ne confirme ni la méthode ni les conclusions de l’étude, et il ne compte pas comme une seconde source scientifique indépendante.

Les institutions déclarées

University of Miami Dr. John T. Macdonald Foundation Case Western Reserve University Columbia University University of Pennsylvania Boston University Cleveland Clinic Lou Ruvo Brain Institute University of Kentucky The University of Texas Southwestern Medical Center The University of Texas at Austin Johns Hopkins University University of Michigan VA Ann Arbor Healthcare System Geriatric Research Education and Clinical Center Michigan Medicine Jacksonville College Mayo Clinic in Florida University of North Texas University of North Texas Health Science Center Indiana University School of Medicine Indiana University – Purdue University Indianapolis University of Wisconsin–Madison Rush University Medical Center Banner Sun Health Research Institute University of Pittsburgh University of Washington Hope Center for Neurological Disorders VA Puget Sound Health Care System Harvard University Massachusetts General Hospital Mayo Clinic Swedish Medical Center University of California, San Francisco University of California San Diego Duke University University of Kansas Medical Center Icahn School of Medicine at Mount Sinai Washington University in St. Louis University of South Florida USF Health Byrd Alzheimer's Institute Fred Hutch Cancer Center Bruce W. Carter VA Medical Center University of North Carolina at Chapel Hill University of California, Los Angeles University of Southern California Wake Forest University University of California, Irvine Baylor College of Medicine University Memory and Aging Center Columbia University Irving Medical Center University of California, Davis Texas Tech University Texas Tech University Health Sciences Center Mount Sinai Medical Center University of Alabama at Birmingham New York University Emory University Brigham and Women's Hospital Mass General Brigham Children's Hospital of Philadelphia University College London Stanford University Vanderbilt University Medical Center Translational Genomics Research Institute Neurological Surgery University of Washington Medical Center Alzheimer’s Disease Neuroimaging Initiative Albert Einstein College of Medicine Brigham Young University Oregon Health & Science University Portland VA Medical Center Kaiser Permanente Washington Health Research Institute National Center for PTSD Northwestern University Pfizer (United States)The University of Texas at San Antonio Health Science Center University of Colorado Denver Alzheimer's Association University of Arizona Banner Alzheimer’s Institute Arizona Alzheimer’s Consortium Alzheimer's Drug Discovery Foundation University of Toronto Occupational Cancer Research Centre Institute for Neurodegenerative Disorders The University of Texas Health Science Center at Houston University of Cambridge Texas A&M Health Science Center Baylor Scott & White Health Texas A&M University Yale University Renaissance Computing Institute

Une affiliation ne permet pas de déduire la nationalité d’un auteur.

Les sujets associés

Genetic Associations and EpidemiologyEpigenetics and DNA MethylationBioinformatics and Genomic Networks

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