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Assessment of the genetic variance of late-onset Alzheimer's disease

2016; Elsevier BV; Volume: 41; Linguagem: Inglês

10.1016/j.neurobiolaging.2016.02.024

1558-1497

Perry G. Ridge, Kaitlyn B. Hoyt, Kevin L. Boehme, Shubhabrata Mukherjee, Paul K. Crane, Jonathan L. Haines, Richard Mayeux, Lindsay A. Farrer, Margaret A. Pericak‐Vance, Gerard D. Schellenberg, John S. K. Kauwe, Perrie M. Adams, Marilyn S. Albert, Roger L. Albin, Liana G. Apostolova, Steven E. Arnold, Sanjay Asthana, Craig Atwood, Clinton T. Baldwin, Robert C. Barber, M. Michael Barmada, Lisa L. Barnes, Sandra Barral, Thomas G. Beach, James T. Becker, Gary W. Beecham, Duane Beekly, David A. Bennett, Eileen H. Bigio, Thomas D. Bird, Deborah Blacker, Bradley F. Boeve, James D. Bowen, Adam Boxer, James R. Burke, Jeffrey M. Burns, Joseph D. Buxbaum, Nigel J. Cairns, Laura B. Cantwell, Chuanhai Cao, Chris Carlson, Cynthia M. Carlsson, Regina M. Carney, Minerva M. Carrasquillo, Steven L. Carroll, Helena C. Chui, David G. Clark, Jason J. Corneveaux, Paul K. Crane, David H. Cribbs, Elizabeth Crocco, Carlos Cruchaga, Philip L. De Jager, Charles DeCarli, F. Yesim Demirci, Malcolm Dick, Dennis W. Dickson, Rachelle S. Doody, Ranjan Duara, Nilüfer Ertekin‐Taner, Denis A. Evans, Kelley Faber, Thomas Fairchild, Kenneth B. Fallon, David W. Fardo, Martin R. Farlow, Steven H. Ferris, Tatiana M. Foroud, Matthew P. Frosch, Douglas Galasko, Marla Gearing, Daniel H. Geschwind, Bernardino Ghetti, John R. Gilbert, Alison Goate, Neill R. Graff‐Radford, Robert C. Green, John H. Growdon, Hákon Hákonarson, Ronald L. Hamilton, Kara L. Hamilton‐Nelson, John Hardy, Lindy E. Harrell, Lawrence S. Honig, Ryan Huebinger, Matthew J. Huentelman, Christine M. Hulette, Bradley T. Hyman, Gail P. Jarvik, Gregory A. Jicha, Lee‐Way Jin, Gyungah Jun, M. Ilyas Kamboh, Anna Karydas, Mindy J. Katz, John S. K. Kauwe, Jonathan Kaye, Ronald Kim, Neil W. Kowall, Joel H. Kramer, Walter A. Kukull, Brian W. Kunkle, Frank M. LaFerla, James J. Lah, Eric B. Larson, James B. Leverenz, Allan I. Levey, Ge Li, Andrew P. Lieberman, Chiao‐Feng Lin, Richard B. Lipton, Oscar L. López, Kathryn L. Lunetta, Constantine G. Lyketsos, Wendy J. Mack, Daniel Marson, Eden R. Martin, 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, Thomas J. Montine, John C. Morris, Shubhabrata Mukherjee, Jill R. Murrell, Amanda Myers, Adam C. Naj, Sid E. O’Bryant, John Olichney, V. Shane Pankratz, Joseph E. Parisi, Amanda Partch, Henry L. Paulson, William Perry, Elaine R. Peskind, Ronald C. Petersen, Aimee Pierce, Wayne W. Poon, Huntington Potter, Joseph F. Quinn, Ashok Raj, Murray A. Raskind, Eric M. Reiman, ‌Barry Reisberg, Joan Reisch, Christiane Reitz, 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, Peter St George‐Hyslop, Robert A. Stern, Russell H. Swerdlow, Rudolph E. Tanzi, Tricia A. Thornton‐Wells, John Q. Trojanowski, Juan C. Troncoso, Debby W. Tsuang, Otto Valladares, Vivianna M. Van Deerlin, Linda J. Van Eldik, Badri N. Vardarajan, Harry V. Vinters, Jean Paul Vonsattel, Li-San Wang, Sandra Weıntraub, Kathleen A. Welsh‐Bohmer, Jens R. Wendland, Kirk C. Wilhelmsen, Jennifer Williamson, Thomas S. Wingo, Ashley R. Winslow, Sarah Wishnek, Randall L. Woltjer, Clinton B. Wright, Chuang‐Kuo Wu, Steven G. Younkin, Chang‐En Yu, Lei Yu,

GDF15 and Related Biomarkers

Alzheimer's disease (AD) is a complex genetic disorder with no effective treatments. More than 20 common markers have been identified, which are associated with AD. Recently, several rare variants have been identified in Amyloid Precursor Protein (APP), Triggering Receptor Expressed On Myeloid Cells 2 (TREM2) and Unc-5 Netrin Receptor C (UNC5C) that affect risk for AD. Despite the many successes, the genetic architecture of AD remains unsolved. We used Genome-wide Complex Trait Analysis to (1) estimate phenotypic variance explained by genetics; (2) calculate genetic variance explained by known AD single nucleotide polymorphisms (SNPs); and (3) identify the genomic locations of variation that explain the remaining unexplained genetic variance. In total, 53.24% of phenotypic variance is explained by genetics, but known AD SNPs only explain 30.62% of the genetic variance. Of the unexplained genetic variance, approximately 41% is explained by unknown SNPs in regions adjacent to known AD SNPs, and the remaining unexplained genetic variance outside these regions.