1. LATE-NC risk alleles (in TMEM106B, GRN, and ABCC9 genes) among persons with African ancestry.
- Author
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Katsumata, Yuriko, Fardo, David W, Shade, Lincoln MP, Bowen, James D, Crane, Paul K, Jarvik, Gail P, Keene, C Dirk, Larson, Eric B, McCormick, Wayne C, McCurry, Susan M, Mukherjee, Shubhabrata, Kowall, Neil W, McKee, Ann C, Honig, Robert A, Lawrence, S, Vonsattel, Jean Paul, Williamson, Jennifer, Small, Scott, Burke, James R, Hulette, Christine M, Welsh-Bohmer, Kathleen A, Gearing, Marla, Lah, James J, Levey, Allan I, Wingo, Thomas S, Apostolova, Liana G, Farlow, Martin R, Ghetti, Bernardino, Saykin, Andrew J, Spina, Salvatore, Albert, Marilyn S, Lyketsos, Constantine G, Troncoso, Juan C, Frosch, Matthew P, Green, Robert C, Growdon, John H, Hyman, Bradley T, Tanzi, Rudolph E, Potter, Huntington, Dickson, Dennis W, Ertekin-Taner, Nilufer, Graff-Radford, Neill R, Parisi, Joseph E, Petersen, Ronald C, Duara, Ranjan, Buxbaum, Joseph D, Goate, Alison M, Sano, Mary, Masurkar, Arjun V, Wisniewski, Thomas, Bigio, Eileen H, Mesulam, Marsel, Weintraub, Sandra, Vassar, Robert, Kaye, Jeffrey A, Quinn, Joseph F, Woltjer, Randall L, Barnes, Lisa L, Bennett, David A, Schneider, Julie A, Yu, Lei, Henderson, Victor, Fallon, Kenneth B, Harrell, Lindy E, Marson, Daniel C, Roberson, Erik D, DeCarli, Charles, Jin, Lee-Way, Olichney, John M, Kim, Ronald, LaFerla, Frank M, Monuki, Edwin, Head, Elizabeth, Sultzer, David, Geschwind, Daniel H, Vinters, Harry V, Chesselet, Marie-Francoise, Galasko, Douglas R, Brewer, James B, Boxer, Adam, Karydas, Anna, Kramer, Joel H, Miller, Bruce L, Rosen, Howard J, Seeley, William W, Burns, Jeffrey M, Swerdlow, Russell H, Abner, Erin, Van Eldik, Linda J, Albin, Roger L, Lieberman, Andrew P, Paulson, Henry L, Arnold, Steven E, Trojanowski, John Q, Van Deerlin, Vivianna M, Hamilton, Ronald L, Kamboh, M Ilyas, Lopez, Oscar L, and Becker, James T
- Subjects
Biomedical and Clinical Sciences ,Neurosciences ,Clinical Sciences ,Aging ,Prevention ,Neurodegenerative ,Acquired Cognitive Impairment ,Alzheimer's Disease ,Dementia ,Minority Health ,Health Disparities ,Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD) ,Brain Disorders ,Genetics ,2.1 Biological and endogenous factors ,Humans ,Alleles ,Polymorphism ,Single Nucleotide ,Alzheimer Disease ,TDP-43 Proteinopathies ,Progranulins ,Membrane Proteins ,Nerve Tissue Proteins ,Sulfonylurea Receptors ,Alzheimer’s Disease Genetics Consortium ,KCNMB2 ,Diversity ,Epidemiology ,FTLD ,Genome-Wide Association Studies ,KATP ,Neurology & Neurosurgery ,Clinical sciences - 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.
- Published
- 2023