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LATE-NC risk alleles (in TMEM106B, GRN, and ABCC9 genes) among persons with African ancestry

2023; Oxford University Press; Volume: 82; Issue: 9 Linguagem: Inglês

10.1093/jnen/nlad059

1554-6578

Yuriko Katsumata, David W. Fardo, Lincoln MP Shade, James D. Bowen, Paul K. Crane, Gail P. Jarvik, C. Dirk Keene, Eric B. Larson, Wayne C. McCormick, Susan M. McCurry, Shubhabrata Mukherjee, Neil W. Kowall, Ann C. McKee, Robert A Honig, Sandra Lawrence, Jean Paul Vonsattel, Jennifer Williamson, Scott A. Small, James R. Burke, Christine M. Hulette, Kathleen A. Welsh‐Bohmer, Marla Gearing, James J. Lah, Allan I. Levey, Thomas S. Wingo, Liana G. Apostolova, Martin R. Farlow, Bernardino Ghetti, Andrew J. Saykin, Salvatore Spina, Marilyn S. Albert, Constantine G. Lyketsos, Juan C. Troncoso, Matthew P. Frosch, Robert C. Green, John H. Growdon, Bradley T. Hyman, Rudolph E. Tanzi, Huntington Potter, Dennis W. Dickson, Nilüfer Ertekin‐Taner, Neill R. Graff‐Radford, Joseph E. Parisi, Ronald Petersen, Ranjan Duara, Joseph D. Buxbaum, Alison Goate, Mary Sano, Arjun V. Masurkar, Thomas Wısnıewskı, Eileen H. Bigio, Marsel Mesulam, Sandra Weıntraub, Robert Vassar, Jeffrey Kaye, Joseph F. Quinn, Randall L. Woltjer, Lisa L. Barnes, David A. Bennett, Julie A. Schneider, Lei Yu, Victor W. Henderson, Kenneth B. Fallon, Lindy E. Harrell, Daniel Marson, Erik D. Roberson, Charles DeCarli, Lee‐Way Jin, John Olichney, Ronald Kim, Frank M. LaFerla, Edwin S. Monuki, Elizabeth Head, David L. Sultzer, Daniel H. Geschwind, Harry V. Vinters, Marie‐Françoise Chesselet, Douglas Galasko, James B. Brewer, Adam Boxer, Anna Karydas, Joel H. Kramer, Bruce L. Miller, Howard J. Rosen, William W. Seeley, Jeffrey M. Burns, Russell H. Swerdlow, Erin L. Abner, David W. Fardo, Linda J. Van Eldik, Roger L. Albin, Andrew P. Lieberman, Henry L. Paulson, Steven E. Arnold, John Q. Trojanowski, Vivianna M. Van Deerlin, Ronald L. Hamilton, M. Ilyas Kamboh, Oscar L. López, James T. Becker, Chuanhai Cao, Ashok Raj, Amanda Smith, Helena C. Chui, Carol A. Miller, John M. Ringman, Lon S. Schneider, Thomas D. Bird, Joshua A. Sonnen, Chang‐En Yu, Thomas J. Grabowski, Elaine R. Peskind, Murray A. Raskind, Ge Li, Debby W. Tsuang, Sanjay Asthana, Craig Atwood, Cynthia M. Carlsson, Mark A. Sager, Nathaniel A. Chin, Suzanne Craft, Nigel J. Cairns, John C. Morris, Carlos Cruchaga, Stephen M. Strittmatter, Eric M. Reiman, Thomas G. Beach, Matthew J. Huentelman, John Hardy, Amanda Myers, John Kauwe, Hákon Hákonarson, Deborah Blacker, Thomas J. Montine, Clinton T. Baldwin, Lindsay A. Farrer, Gyungah Jun, Kathryn L. Lunetta, William S. Bush, Jonathan L. Haines, Alan J. Lerner, Xiongwei Zhou, Sandra Barral, Christiane Reitz, Badri N. Vardarajan, Richard Mayeux, Gary W. Beecham, Regina M. Carney, Michael L. Cuccaro, John R. Gilbert, Kara L. Hamilton‐Nelson, Brian W. Kunkle, Eden R. Martin, Margaret A Pericak‐Vance, Jeffery M. Vance, Laura B. Cantwell, Amanda P Kuzma, John Malamon, Adam C. Naj, Liming Qu, Gerard D. Schellenberg, Otto Valladares, Li‐San Wang, Yi Zhao, James B. Leverenz, Philip L. De Jager, Denis A. Evans, Mindy J. Katz, Richard B. Lipton, Bradley F. Boeve, Mariet Allen, Minerva M. Carrasquillo, Steven G. Younkin, Walter A. Kukull, Kelley Faber, Tatiana M. Foroud, Valory Pavlik, Paul J. Massman, Eveleen Darby, Monica Rodriguear, Aisha Khaleeq, Donald R. Royall, Alan Stevens, Marcia G. Ory, John C. DeToledo, Henrick Wilms, Kim Johnson, Victòria Aurora Ferrer Pérez, Michelle L. Hernandez, Kirk C. Wilhelmsen, Jeffrey L. Tilson, Scott Chasse, Robert C. Barber, Thomas Fairchild, Sid E. O’Bryant, Janice Knebl, James Hall, Leigh Johnson, Douglas Mains, Lisa Alvarez, Adriana C. Gamboa, David Paydarfar, John Bertelson, Martin Woon, Gayle Ayres, Alyssa Aguirre, Raymond F. Palmer, Marsha J. Polk, Perrie M. Adams, Ryan Huebinger, Joan Reisch, Roger N. Rosenberg, C. Munro Cullum, Benjamin J. Williams, Mary Quiceno, Linda S. Hynan, Janet L. Smith, Barb Davis, Trung Dung Nguyen, Ekaterina Rogaeva, Peter St George‐Hyslop, Peter T. Nelson,

Genetics and Neurodevelopmental Disorders

Abstract Limbic-predominant age-related TDP-43 encephalopathy (LATE) affects approximately one-third of older individuals and is associated with cognitive impairment. However, there is a highly incomplete understanding of the genetic determinants of LATE neuropathologic changes (LATE-NC) in diverse populations. The defining neuropathologic feature of LATE-NC is TDP-43 proteinopathy, often with comorbid hippocampal sclerosis (HS). In terms of genetic risk factors, LATE-NC and/or HS are associated with single nucleotide variants (SNVs) in 3 genes—TMEM106B (rs1990622), GRN (rs5848), and ABCC9 (rs1914361 and rs701478). We evaluated these 3 genes in convenience samples of individuals of African ancestry. The allele frequencies of the LATE-associated alleles were significantly different between persons of primarily African (versus European) ancestry: In persons of African ancestry, the risk-associated alleles for TMEM106B and ABCC9 were less frequent, whereas the risk allele in GRN was more frequent. We performed an exploratory analysis of data from African-American subjects processed by the Alzheimer’s Disease Genomics Consortium, with a subset of African-American participants (n = 166) having corroborating neuropathologic data through the National Alzheimer’s Coordinating Center (NACC). In this limited-size sample, the ABCC9/rs1914361 SNV was associated with HS pathology. More work is required concerning the genetic factors influencing non-Alzheimer disease pathology such as LATE-NC in diverse cohorts.