Novel Alzheimer Disease Risk Loci and Pathways in African American Individuals Using the African Genome Resources Panel

作者：Brian W. Kunkle, Michael A. Schmidt, Hans‐Ulrich Klein, Adam C. Naj, Kara L. Hamilton‐Nelson, Eric B. Larson, Denis A. Evans, Phil L. De Jager, Paul K. Crane, Joseph D. Buxbaum, Nilüfer Ertekin‐Taner, Lisa L. Barnes, M. Daniele Fallin, Jennifer J. Manly, Rodney C.P. Go, Thomas O. Obisesan, M. Ilyas Kamboh, David A. Bennett, Kathleen Hall, Alison Goate, Tatiana M. Foroud, Eden R. Martin, Li‐San Wang, Goldie S. Byrd, Lindsay A. Farrer, Jonathan L. Haines, Gerard D. Schellenberg, Richard Mayeux, Margaret A. Pericak‐Vance, Christiane Reitz, Erin L. Abner, M. Adams Perrie, L. Albin Roger, G Apostolova Liana, Eschrich Steven, S Craig, T. Baldwin Clinton, C. Barber Robert, Sandra Barral, Gunther Thomas, T. James, W. Beecham Gary, H. Bigio Eileen, D. Thomas, Deborah Blacker, F. Boeve Bradley, D. Bowen James, Adam Boxer, R. Burke James, Morris Jeffrey, J Cairns Nigel, Chuanhai Cao, M. Carlsson Cynthia, M. Carney Regina, M. Carrasquillo Minerva, Hugh-Jones David, Carlos Cruchaga, Malcom Dick, Dennis, W. Dickson, Rachelle S. Doody, Ranjan Duara, M. Faber Kelley, Jaya Thomas, B. Kenneth, W. Fardo David, Roger Martin, Steven H. Ferris, P. Frosch Matthew, R. Galasko Douglas, Marla Gearing, Hervé Daniel, Bernardino Ghetti, John, R. Gilbert, C. Green Robert, Harding John, Håkon Håkonarson, L. Hamilton Ronald, John Hardy, E. Harrell Lindy, Steve Lawrence, Mary Ryan, J. Huentelman Matthew, M Hulette Christine, P. Jarvik Gail, Lee‐Way Jin, Anna Karydas, J. Katz Mindy, S. John, C. Dirk Keene, Ronald Kim, H. Kramer Joel, J. Lah James, Yuk Yee Leung, Ge Li, Peter Andrew, B. Richard, G. Lyketsos Constantine, John Malamon, Chammiran Daniel, Frank Martiniuk, Eliezer Masliah, C. McCormick Wayne, M Susan, Nesbit M Andrew, Stefan McDonough, Canfield Ann., Marsel Mesulam, L. Miller Bruce, A. Miller Carol, J. Montine Thomas, Shubhabrata Mukherjee, J. Myers Amanda, Eric Sid, M. Olichney John, E. Parisi Joseph, Elaine R. Peskind, Aimee Pierce, W. Poon Wayne, Huntington Potter, Liming Qu, F. Quinn Joseph, Ashok Raj, Murray A. Raskind, ‌Barry Reisberg, Joan, S. Reisch, M. Ringman John, D. Roberson Erik, Ekaterina Rogaeva, J. Rosen Howard, R. Royall Donald, A. Sager Mark, A. Schneider Julie, Su Lon, W. Seeley William, Scott A. Small, Joshua, A. Sonnen, Salvatore Spina, Peter St George‐Hyslop, Aiko Robert, E. Tanzi Rudolph, Caballero Juan, W. Tsuang Debby, Otto Valladares, M. Van Deerlin Vivianna, Nabeel Badri, Vanessa Harry, Jean Paul Vonsattel, Sandra Weıntraub, A Welsh-Bohmer Kathleen, C W Kirk, Jennifer Williamson, SubinVarghese Thomas, Linnell B. Randall, Chuang‐Kuo Wu, G. Younkin Steven, Lei Yu, Chang‐En Yu, Yi Zhao, Neill R. Graff‐Radford, Izri Martinez, Temitope Ayodele, Mark W. Logue, Laura B. Cantwell, Melissa Jean‐Francois, Amanda Kuzma, Lonnie D. Adams, Jeffery M. Vance, Michael L. Cuccaro, Jaeyoon Chung, Jesse Mez, Kathryn L. Lunetta, Gyungah Jun, Oscar L. López, Hugh C. Hendrie, Eric M. Reiman, Neil W. Kowall, James B. Leverenz, Scott A. Small, Allan I. Levey, Todd E. Golde, Andrew J. Saykin, Takiyah D. Starks, Marilyn S. Albert, Bradley T. Hyman, Ronald Petersen, Mary Sano, Thomas Wısnıewskı, Robert Vassar, Jeffrey A. Kaye, Victor W. Henderson, Charles DeCarli, Frank M. LaFerla, James B. Brewer, Bruce L. Miller, Russell H. Swerdlow, Linda J. Van Eldik, Henry L. Paulson, John Q. Trojanowski, Helena C. Chui, Roger N. Rosenberg, Suzanne Craft, Thomas J. Grabowski, Sanjay Asthana, John C. Morris, Stephen M. Strittmatter, Walter A. Kukull · 发表于：JAMA Neurology · 年份：2020 · DOI：10.1001/jamaneurol.2020.3536 · 被引用次数：284 · 研究领域：Alzheimer's disease research and treatments、Neuroinflammation and Neurodegeneration Mechanisms、Dementia and Cognitive Impairment Research

Importance: Compared with non-Hispanic White individuals, African American individuals from the same community are approximately twice as likely to develop Alzheimer disease. Despite this disparity, the largest Alzheimer disease genome-wide association studies to date have been conducted in non-Hispanic White individuals. In the largest association analyses of Alzheimer disease in African American individuals, ABCA7, TREM2, and an intergenic locus at 5q35 were previously implicated. Objective: To identify additional risk loci in African American individuals by increasing the sample size and using the African Genome Resource panel. Design, Setting, and Participants: This genome-wide association meta-analysis used case-control and family-based data sets from the Alzheimer Disease Genetics Consortium. There were multiple recruitment sites throughout the United States that included individuals with Alzheimer disease and controls of African American ancestry. Analysis began October 2018 and ended September 2019. Main Outcomes and Measures: Diagnosis of Alzheimer disease. Results: A total of 2784 individuals with Alzheimer disease (1944 female [69.8%]) and 5222 controls (3743 female [71.7%]) were analyzed (mean [SD] age at last evaluation, 74.2 [13.6] years). Associations with 4 novel common loci centered near the intracellular glycoprotein trafficking gene EDEM1 (3p26; P = 8.9 × 10-7), near the immune response gene ALCAM (3q13; P = 9.3 × 10-7), within GPC6 (13q31; P = 4.1 × 10-7),...