Citations 4
Transethnic genome‐wide scan identifies novel Alzheimer's disease loci
Jun, Gyungah , Chung, Jaeyoon , Beecham, Gary W. , Bennett, David A. , Buxbaum, Joseph D. , Byrd, Goldie S. , Carrasquillo, Minerva M., Crane, Paul K. , Cruchaga, Carlos , Jager, Philip L. De , Ertekin‐Taner, Nilüfer , Evans, Denis A., Fallin, M. Danielle, Friedland, Robert P. , Goate, Alison , Graff‐Radford, Neill R. , Hendrie, Hugh C. , Hall, Kathleen, Hamilton‐Nelson, Kara L., Kukull, Walter A. , Kunkle, Brian W. , Kuwano, Ryozo, Larson, Eric B., Martin, Eden R. , Montine, Thomas J. , Reiman, Eric M. , Reitz, Christiane, Sherva, Richard , George‐Hyslop, Peter St , Thornton, Timothy, Younkin, Steven G., Wang, Li‐San , Wendlund, Jens R., Winslow, Ashley R. , Adams, Perrie M. , Albert, Marilyn S. , Albin, Roger L. , Apostolova, Liana G. , Arnold, Steven E. , Asthana, Sanjay , Atwood, Craig , Barmada, Michjael M, Beach, Thomas G. , Bigio, Eileen H. , Bird, Thomas D., Blacker, Deborah , Bowen, James D. , Boxer, Adam, Cairns, Nigel J. , Cao, Chuanhai , Carlson, Chris , Carlsson, Cynthia M., Carney, Regina M., Carroll, Steven L. , Chui, Helena C., Clark, David G., Corneveaux, Jason J., Cribbs, David H. , DeKosky, Steven T. , Demirci, F. Yesim , Dick, Malcolm, Doody, Rachelle S., Duara, Ranjan , Faber, Kelley , Fairchild, Thomas, Fallon, Kenneth B., Farlow, Martin R. , Frosch, Matthew P. , Gearing, Marla , Geschwind, Daniel H. , Gilbert, John R., Glass, Jonathan D. , Growdon, John H., Håkonarson, Håkon , Hamilton, Ronald L. , Hardy, John , Harrell, Lindy E., Huentelman, Matthew J. , Hulette, Christine M., Jarvik, Gail P. , Jicha, Gregory A. , Jin, Lee‐Way, Karydas, Anna, Koo, Edward H. , Kowall, Neil W. , Kramer, Joel H. , LaFerla, Frank M. , Leverenz, James B. , Ge, Li , Lieberman, Andrew P. , Lin, Chiao‐Feng , Lyketsos, Constantine G. , Mack, Wendy J. , Marson, Daniel , Martiniuk, Frank , Mash, Deborah C. , Masliah, Eliezer , McCormick, Wayne C., McKee, Ann C. , Mesulam, Marsel, Miller, Carol A., Miller, Joshua W., Morris, John C. , Murrell, Jill R. , Olichney, John , Parisi, Joseph E., Partch, Amanda, Paulson, Henry L. , Peskind, Elaine R. , Petersen, Ronald , Pierce, Aimee, Poon, Wayne W. , Raj, Ashok , Raskind, Murray A. , Reisch, Joan, Ringman, John M. , Rosen, Howard J., Rosenberg, Roger N., Royall, Donald R., Sager, Mark A., Sano, Mary , Saykin, Andrew J. , Schneider, Lon S. , Smith, Amanda , Sonnen, Joshua A. , Tanzi, Rudolph E. , Thornton‐Wells, Tricia A., Trojanowski, John Q. , Troncoso, Juan C. , Vinters, Harry V. , Vonsattel, Jean Paul, Weıntraub, Sandra , Wishnek, Sarah, Woltjer, Randall L. , Wright, Clinton B., Wu, Chuang‐Kuo, Yu, Chang‐En , Yu, Lei , Haines, Jonathan L. , Mayeux, Richard , Pericak‐Vance, Margaret A. , Schellenberg, Gerard, Lunetta, Kathryn L. , Farrer, Lindsay A. , Bennett, David A. , Mez, Jesse , Barber, Robert C. , Carrasquillo, Minerva M. , Cruchaga, Carlos , Foroud, Tatiana , Hamilton‐Nelson, Kara L. , Inzelberg, Rivka , Kamboh, M. Ilyas , Kauwe, John S. K. , Logue, Mark W. , Manly, Jennifer J. , Mukherjee, Shubhabrata , Naj, Adam Christian , Sherva, Richard , Vardarajan, Badri Narayan , Barnes, Lisa L. , Becker, James T. , Boeve, Bradley F. , Burke, James R. , Carlsson, Cynthia M. , Chui, Helena C. , Crocco, Elizabeth , DeCarli, Charles , Dickson, Dennis W. , Duara, Ranjan , Ferris, Steven H. , Galasko, Douglas , Ghetti, Bernardino , Green, Robert C. , Head, Elizabeth , Honig, Lawrence S. , Huebinger, Ryan , Hyman, Bradley T. , Kaye, Jeffrey , Kim, Ronald , Lah, James J. , Levey, Allan I. , Li, Ge, López, Oscar L. , McCurry, Susan M. , McDavid, Andrew , Mesulam, Marsel M. , Miller, Bruce L. , Myers, Amanda , O’Bryant, Sid E. , Pankratz, V. Shane , Perry, William , Potter, Huntington , Quinn, Joseph F. , Reisberg, Barry , Roberson, Erik D. , Rogaeva, Ekaterina A. , Schneider, Julie A. , Seeley, William W. , Spina, Salvatore , Stern, Robert A. , Tsuang, Debby W. , Deerlin, Vivianna M. Van , Eldik, Linda J. Van , Welsh-Bohmer, Kathleen Anne , Williamson, Jennifer , Zhang, Xiaoling , Hakonarson, Hakon , Saykin, Andrew J , Leverenz, James B , Jarvik, Gail P , Paulson, Henry L , Hardy, John , Morris, John C , Goate, Alison M , Jicha, Gregory A , Sonnen, Joshua
Alzheimer's & Dementia | February 6, 2017 | Volume: 13 | Issue: 7 | Pages: 727-738
Abstract Introduction Genetic loci for Alzheimer's disease (AD) have been identified in whites of European ancestry, but the genetic architecture of AD among other populations is less understood. Methods We conducted a transethnic genome‐wide association study (GWAS) for late‐onset AD in Stage 1 sample including whites of European Ancestry, African‐Americans, Japanese, and Israeli‐Arabs assembled by the Alzheimer's Disease Genetics Consortium. Suggestive results from Stage 1 from novel loci were followed up using summarized results in the International Genomics Alzheimer's Project GWAS dataset. Results Genome‐wide significant (GWS) associations in single‐nucleotide polymorphism (SNP)–based tests ( P < 5 × 10 −8 ) were identified for SNPs in PFDN1/HBEGF , USP6NL/ECHDC3 , and BZRAP1‐AS1 and for the interaction of the (apolipoprotein E) APOE ε4 allele with NFIC SNP. We also obtained GWS evidence ( P < 2.7 × 10 −6 ) for gene‐based association in the total sample with a novel locus, TPBG ( P = 1.8 × 10 −6 ). Discussion Our findings highlight the value of transethnic studies for identifying novel AD susceptibility loci.
Rarity of the Alzheimer Disease–ProtectiveAPPA673T Variant in the United States
Wang, Li-San, Graham, Robert , Crane, Paul K. , Kunkle, Brian W. , Cruchaga, Carlos , Murcia, Josue D. Gonzalez , Cannon‐Albright, Lisa , Baldwin, Clinton T., Blennow, Kaj , Kukull, Walter A. , Faber, Kelley M., Schupf, Nicole , Norton, Maria C. , Tschanz, JoAnn T. , Munger, Ronald G. , Corcoran, Christopher, Lin, Chiao‐Feng , Dombroski, Beth A. , Cantwell, Laura B., Partch, Amanda, Håkonarson, Håkon , George‐Hyslop, Peter St , Goate, Alison , Foroud, Tatiana, Carney, Regina M., Larson, Eric B., Behrens, Timothy W. , Kauwe, John, Haines, Jonathan L. , Farrer, Lindsay A. , Pericak‐Vance, Margaret A. , Mayeux, Richard , Schellenberg, Gerard D., Albert, Marilyn S. , Albin, Roger L. , Apostolova, Liana G. , Arnold, Steven E. , Barber, Robert W., Barmada, M. Michael , Beach, Thomas G. , Beecham, Gary W. , Beekly, Duane, Bennett, David A. , Bigio, Eileen H. , Bird, Thomas D., Blacker, Deborah , Bowen, James D. , Boxer, Adam, Buxbaum, Joseph D. , Cairns, Nigel J. , Cao, Chuanhai , Carlson, Chris , Carroll, Steven L. , Chui, Helena C., Clark, David G., Cribbs, David H. , DeCarli, Charles , DeKosky, Steven T. , Demirci, F. Yesim , Dick, Malcolm, Duara, Ranjan , Ertekin‐Taner, Nilüfer , Fallon, Kenneth B., Farlow, Martin R. , Ferris, Steven H. , Frosch, Matthew P. , Gearing, Marla , Geschwind, Daniel H. , Gilbert, John R., Glass, Jonathan D. , Graff‐Radford, Neill R. , Growdon, John H., Hamilton, Ronald L. , Hamilton‐Nelson, Kara L., Harrell, Lindy E., Hulette, Christine M., Jicha, Gregory A. , Jin, Lee‐Way, Jun, Gyungah , Kamboh, M. Ilyas , Karydas, Anna, Koo, Edward H. , Kowall, Neil W. , Kramer, Joel H. , Kramer, Patricia, LaFerla, Frank M. , Leverenz, James B. , Lieberman, Andrew P. , Lunetta, Kathryn L. , Lyketsos, Constantine G. , Mack, Wendy J. , Marson, Daniel , Martin, Eden R. , Martiniuk, Frank , Mash, Deborah C. , Masliah, Eliezer , McCormick, Wayne C., McKee, Ann C. , Miller, Carol A., Miller, Joshua W., Montine, Thomas J. , Morris, John C. , Murrell, Jill R. , Olichney, John , Parisi, Joseph E., Peskind, Elaine R. , Petersen, Ronald , Pierce, Aimee, Poon, Wayne W. , Raj, Ashok , Raskind, Murray A. , Reiman, Eric M. , Reisberg, Barry , Reitz, Christiane , Ringman, John M. , Rosen, Howard J., Rosenberg, Roger N., Sano, Mary , Saykin, Andrew J. , Schneider, Lon S. , Smith, Amanda , Sonnen, Joshua A. , Stern, Robert A. , Tanzi, Rudolph E. , Thornton‐Wells, Tricia A., Trojanowski, John Q. , Troncoso, Juan C. , Tsuang, Debby W. , Vinters, Harry V. , Vonsattel, Jean Paul, Weıntraub, Sandra , Wishnek, Sarah, Woltjer, Randall L. , Wright, Clinton B., Younkin, Steven G., Yu, Chang‐En , Yu, Lei , DeCarli, Charles , Wang, Li-San, Naj, Adam Christian , Cruchaga, Carlos , Zetterberg, Henrik , Rogaeva, Ekaterina A. , Valladares, Otto , Green, Robert C. , Barnes, Lisa L. , Becker, James T. , Boeve, Bradley F. , Burke, James R. , Chui, Helena C. , Crocco, Elizabeth , Dickson, Dennis W. , Duara, Ranjan , Galasko, Douglas , Ganguli, Mary , Ghetti, Bernardino , Hamilton‐Nelson, Kara L. , Head, Elizabeth , Honig, Lawrence S. , Hyman, Bradley T. , Jarvik, Gail P. , Kaye, Jeffrey , Kim, Ronald , Lah, James J. , Levey, Allan I. , Li, Ge , López, Oscar L. , McCurry, Susan M. , McDavid, Andrew , Mesulam, Marsel M. , Miller, Bruce L. , Perry, William , Potter, Huntington , Quinn, Joseph F. , Roberson, Erik D. , Schneider, Julie A. , Seeley, William W. , Spina, Salvatore , Deerlin, Vivianna M. Van , Eldik, Linda J. Van , Vardarajan, Badri Narayan , Welsh-Bohmer, Kathleen Anne , Williamson, Jennifer , Bennett, David A. , Hakonarson, Hakon , Saykin, Andrew J , Leverenz, James B , Cannon-Albright, Lisa A , Stern, Robert A , Morris, John C , Goate, Alison M , Jicha, Gregory A , Sonnen, Joshua
JAMA Neurology | December 22, 2014 | Volume: 72 | Issue: 2 | Pages: 209
Effects of Multiple Genetic Loci on Age at Onset in Late-Onset Alzheimer Disease
Jun, Gyungah , Reitz, Christiane, Kunkle, Brian W. , Park, Yo Son, Beecham, Gary W. , Rajbhandary, Ruchita, Hamilton‐Nelson, Kara L., Wang, Li-San, Kauwe, John, Huentelman, Matthew J. , Bird, Thomas D., Baldwin, Clinton T., Jarvik, Gail P. , Crane, Paul K. , Barmada, M. Michael , Demirci, F. Yesim , Cruchaga, Carlos , Kramer, Patricia L., Ertekin‐Taner, Nilüfer , Hardy, John , Graff‐Radford, Neill R. , Larson, Eric B., George‐Hyslop, Peter St , Buxbaum, Joseph D. , Evans, Denis A., Lunetta, Kathryn L. , Kamboh, M. Ilyas , Saykin, Andrew J. , Reiman, Eric M. , Jager, Philip L. De , Morris, John C. , Montine, Thomas J. , Goate, Alison , Blacker, Deborah , Tsuang, Debby W. , Håkonarson, Håkon , Kukull, Walter A. , Foroud, Tatiana, Martin, Eden R. , Haines, Jonathan L. , Mayeux, Richard , Farrer, Lindsay A. , Schellenberg, Gerard D., Pericak‐Vance, Margaret A. , Albert, Marilyn S. , Albin, Roger L. , Apostolova, Liana G. , Arnold, Steven E. , Barber, Robert W., Beach, Thomas G. , Beekly, Duane, Bigio, Eileen H. , Bowen, James D. , Boxer, Adam, Cairns, Nigel J. , Cantwell, Laura B., Cao, Chuanhai , Carlson, Chris , Carney, Regina M., Carrasquillo, Minerva M., Carroll, Steven L. , Chui, Helena C., Clark, David G., Corneveaux, Jason J., Cribbs, David H. , DeCarli, Charles , DeKosky, Steven T. , Dick, Malcolm, Duara, Ranjan , Faber, Kelley M., Fallon, Kenneth B., Farlow, Martin R. , Ferris, Steven H. , Frosch, Matthew P. , Gearing, Marla , Geschwind, Daniel H. , Gilbert, John R., Glass, Jonathan D. , Growdon, John H., Hamilton, Ronald L. , Harrell, Lindy E., Hulette, Christine M., Jicha, Gregory A. , Jin, Lee‐Way, Karydas, Anna, Koo, Edward H. , Kowall, Neil W. , Kramer, Joel H. , LaFerla, Frank M. , Leverenz, James B. , Li, Ge , Lieberman, Andrew P. , Lin, Chiao‐Feng , Lyketsos, Constantine G. , Mack, Wendy J. , Martiniuk, Frank , Mash, Deborah C. , Masliah, Eliezer , McCormick, Wayne C., McKee, Ann C. , Miller, Carol A., Miller, Joshua W., Murrell, Jill R. , Olichney, John , Parisi, Joseph E., Paulson, Henry L. , Peskind, Elaine R. , Petersen, Ronald , Pierce, Aimee, Poon, Wayne W. , Raj, Ashok , Raskind, Murray A. , Reisberg, Barry , Ringman, John M. , Rosen, Howard J., Rosenberg, Roger N., Sano, Mary , Schneider, Lon S. , Smith, Amanda , Sonnen, Joshua A. , Stern, Robert A. , Tanzi, Rudolph E. , Thornton‐Wells, Tricia A., Trojanowski, John Q. , Troncoso, Juan C. , Vinters, Harry V. , Vonsattel, Jean Paul, Weıntraub, Sandra , Wishnek, Sarah, Woltjer, Randall L. , Wright, Clinton B., Younkin, Steven G., Yu, Chang‐En , Yu, Lei, Bennett, David A. , DeCarli, Charles , Pankratz, Vernon S, Naj, Adam Christian , Perry, William , Hamilton‐Nelson, Kara L. , Wang, Li-San, Myers, Amanda , Boeve, Bradley F. , Rogaeva, Ekaterina A. , Cruchaga, Carlos , Kramer, P. L., Green, Robert C. , Schneider, Julie A. , Bennett, David , Barnes, Lisa L. , Becker, James T. , Burke, James R. , Carrasquillo, Minerva M. , Chui, Helena C. , Crocco, Elizabeth , Dickson, Dennis W. , Duara, Ranjan , Galasko, Douglas , Ganguli, Mary , Ghetti, Bernardino , Head, Elizabeth , Honig, Lawrence S. , Hyman, Bradley T. , Kaye, Jeffrey , Kim, Ronald , Lah, James J. , Levey, Allan I. , López, Oscar L. , McCurry, Susan M. , McDavid, Andrew , Mesulam, Marsel M. , Miller, Bruce L. , Pankratz, V. Shane , Potter, Huntington , Quinn, Joseph F. , Roberson, Erik D. , Seeley, William W. , Spina, Salvatore , Valladares, Otto , Deerlin, Vivianna M. Van , Eldik, Linda J. Van , Vardarajan, Badri Narayan , Welsh-Bohmer, Kathleen Anne , Williamson, Jennifer , Bennett, David A. , Hakonarson, Hakon , Saykin, Andrew J , Leverenz, James B , Jarvik, Gail P , Paulson, Henry L , Stern, Robert A , Hardy, John , Morris, John C , Goate, Alison M , Jicha, Gregory A , Sonnen, Joshua
JAMA Neurology | September 8, 2014 | Volume: 71 | Issue: 11 | Pages: 1394
Phosphorylation of dedicator of cytokinesis 1 (Dock180) at tyrosine residue Y722 by Src family kinases mediates EGFRvIII-driven glioblastoma tumorigenesis
Hu, Bo , Jarzynka, Michael J., Li, Yanxin , Keezer, Susan, Johns, Terrance G. , Tang, Careen K., Hamilton, Ronald L. , Fenton, Tim R. , Cheng, Tao , Furnari, Frank B. , Cavenee, Webster K. , Cheng, Shi‐Yuan , Feng, Haizhong , Vuori, Kristiina , Nishikawa, Ryo , Sarkaria, Jann N. , Cheng, Shi-Yuan , Fenton, Tim R
Proceedings of the National Academy of Sciences | February 8, 2012 | Volume: 109 | Issue: 8 | Pages: 3018-3023
Glioblastoma, the most common primary malignant cancer of the brain, is characterized by rapid tumor growth and infiltration of tumor cells throughout the brain. These traits cause glioblastomas to be highly resistant to current therapies with a resultant poor prognosis. Although aberrant oncogenic signaling driven by signature genetic alterations, such as EGF receptor (EGFR) gene amplification and mutation, plays a major role in glioblastoma pathogenesis, the responsible downstream mechanisms remain less clear. Here, we report that EGFRvIII (also known as ΔEGFR and de2-7EGFR), a constitutively active EGFR mutant that is frequently co-overexpressed with EGFR in human glioblastoma, promotes tumorigenesis through Src family kinase (SFK)-dependent phosphorylation of Dock180, a guanine nucleotide exchange factor for Rac1. EGFRvIII induces phosphorylation of Dock180 at tyrosine residue 722 (Dock180 Y722 ) and stimulates Rac1-signaling, glioblastoma cell survival and migration. Consistent with this being causal, siRNA knockdown of Dock180 or expression of a Dock180 Y722F mutant inhibits each of these EGFRvIII-stimulated activities. The SFKs, Src, Fyn, and Lyn, induce phosphorylation of Dock180 Y722 and inhibition of these SFKs by pharmacological inhibitors or shRNA depletion markedly attenuates EGFRvIII-induced phosphorylation of Dock180 Y722 , Rac1 activity, and glioblastoma cell migration. Finally, phosphorylated Dock180 Y722 is coexpressed with EGFRvIII and phosphorylated Src Y418 in clinical specimens, and such coexpression correlates with an extremely poor survival in glioblastoma patients. These results suggest that targeting the SFK-p-Dock180 Y722 -Rac1 signaling pathway may offer a novel therapeutic strategy for glioblastomas with EGFRvIII overexpression.