Citations 3
Copy Number Variation and Haplotype Analysis of 17q21.31 Reveals Increased Risk Associated with Progressive Supranuclear Palsy and Gene Expression Changes in Neuronal Cells
Wang, Hui , Chang, Timothy S. , Dombroski, Beth A. , Cheng, Po‐Liang , Si, Yaqin , Tucci, Albert , Patil, Vishakha, Valiente‐Banuet, Leopoldo , Li, Chong , Farrell, Kurt , Molina‐Porcel, Laura , Rajput, Alex , Gearing, Marla , Newell, Kathy L. , Rábano‐Gutierrez, Alberto, Oertel, Wolfgang H. , Respondek, Gesine , Stamelou, María , Arzberger, Thomas , Roeber, Sigrun, Müller, Ulrich , Pástor, Pau , Ber, Isabelle Le, Beach, Thomas G. , Litvan, Irene , Rademakers, Rosa , Ross, Owen A. , Boxer, Adam L. , Seeley, Willian W., Lee, Edward B. , Silva, Rohan de , Crary, John F. , Goate, Alison , Friedman, Jeffrey S., Compta, Yaroslau , Coppola, Giovanni , Wang, Li‐San , Group, PSP Genetics Study, Tzeng, Jung‐Ying , Geschwind, Daniel H. , Schellenberg, Gerard D. , Si, Ya-Qin , Mclean, Catriona , Molina-Porcel, Laura , Rajput, Alex , Deyn, Peter Paul De , Le Bastard, Nathalie , Gearing, Marla , Donker Kaat, Laura , Van Swieten, John C , Ghetti, Bernardino F , Troakes, Claire , de Yébenes, Justo G , Meller, Tina , Oertel, Wolfgang H , Respondek, Gesine , Hopfner, Franziska , Pastor, Pau , Brice, Alexis , Dürr, Alexandra , Beach, Thomas G , Serrano, Geidy E , Hazrati, Lili‐Naz , Litvan, Irene , Ross, Owen A , Galasko, Douglas , Boxer, Adam , Miller, Bruce L , Deerlin, Vivianna M. Van , Lee, Edward B , White, Charles L , Morris, Huw R , Crary, John F , Goate, Alison M , Leung, Yuk Yee , Wang, Li-San , Dickson, Dennis W , Höglinger, Günter U , Tzeng, Jung-Ying , Schellenberg, Gerard D , Lee, Wan-Ping , Dombroski, Beth , Farrell, Kurt , McLean, Catriona , Kaat, Laura Donker , Swieten, John C. van , Dopper, Elise G.P. , Ghetti, Bernardino , Troakes, Claire , Müller, Ulrich, Hopfner, Franziska , Brice, Alexis , Ber, Isabelle Le , Serrano, Geidy E. , Galasko, Douglas , Miller, Bruce L. , White, Charles L. , Morris, Huw R. , Naj, Adam Christian , Group, PSP Genetics Study, Dalgard, Clifton L. , Dickson, Dennis W. , Höglinger, Günter U.
Movement Disorders | March 12, 2025 | Volume: 40 | Issue: 5 | Pages: 950-961
AbstractBackgroundThe 17q21.31 region with various structural forms characterized by the H1/H2 haplotypes and three large copy number variations (CNVs) represents the strongest risk locus in progressive supranuclear palsy (PSP).ObjectiveTo investigate the association between CNVs and structural forms on 17q.21.31 with the risk of PSP.MethodsUtilizing whole genome sequencing data from 1684 PSP cases and 2392 controls, the three large CNVs (α, β, and γ) and structural forms within 17q21.31 were identified and analyzed for their association with PSP.ResultsWe found that the copy number of γ was associated with increased PSP risk (odds ratio [OR] = 1.10, P = 0.0018). From H1β1γ1 (OR = 1.21) and H1β2γ1 (OR = 1.24) to H1β1γ4 (OR = 1.57), structural forms of H1 with additional copies of γ displayed a higher risk for PSP. The frequency of the risk sub‐haplotype H1c rises from 1% in individuals with two γ copies to 88% in those with eight copies. Additionally, γ duplication up‐regulates expression of ARL17B, LRRC37A/LRRC37A2, and NSFP1, while down‐regulating KANSL1. Single‐nucleus RNA‐seq of the dorsolateral prefrontal cortex analysis reveals γ duplication primarily up‐regulates LRRC37A/LRRC37A2 in neuronal cells.ConclusionsThe copy number of γ is associated with the risk of PSP after adjusting for H1/H2, indicating that the complex structure at 17q21.31 is an important consideration when evaluating the genetic risk of PSP. © 2025 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
Novel Alzheimer Disease Risk Loci and Pathways in African American Individuals Using the African Genome Resources Panel
Kunkle, Brian W. , Schmidt, Michael A. , Klein, Hans‐Ulrich , Hamilton‐Nelson, Kara L., Larson, Eric B., Evans, Denis A., Jager, Phil L. De, Crane, Paul K. , Buxbaum, Joseph D. , Ertekin‐Taner, Nilüfer , Barnes, Lisa L. , Fallin, M. Daniele , Go, Rodney C.P., Obisesan, Thomas O. , Bennett, David A. , Hall, Kathleen, Goate, Alison , Foroud, Tatiana M., Martin, Eden R. , Wang, Li‐San , Byrd, Goldie S. , Haines, Jonathan L. , Schellenberg, Gerard D., Mayeux, Richard , Pericak‐Vance, Margaret A. , Reitz, Christiane, Perrie, M. Adams, Roger, L. Albin, Liana, G Apostolova, Steven, Eschrich, Craig, S , Clinton, T. Baldwin, Robert, C. Barber, Barral, Sandra, Thomas, Gunther, James, T., Gary, W. Beecham, Eileen, H. Bigio, Thomas, D., Blacker, Deborah, Bradley, F. Boeve, James, D. Bowen, Boxer, Adam, James, R. Burke, Jeffrey, Morris, Nigel, J Cairns, Cynthia, M. Carlsson, Regina, M. Carney, Minerva, M. Carrasquillo, David, Hugh-Jones, Dick, Malcom, Dickson, Dennis, W., Doody, Rachelle S., Duara, Ranjan , Kelley, M. Faber, Thomas, Jaya , Kenneth, B., David, W. Fardo, Martin, Roger, Matthew, P. Frosch, Douglas, R. Galasko, Gearing, Marla , Daniel, Hervé, Gilbert, John, R., Robert, C. Green, John, Harding, Ronald, L. Hamilton, Hardy, John , Lindy, E. Harrell, Lawrence, Steve, Ryan, Mary, Matthew, J. Huentelman, Christine, M Hulette, Gail, P. Jarvik, Jin, Lee‐Way, Karydas, Anna, Mindy, J. Katz, John, S., Joel, H. Kramer, James, J. Lah, Andrew, Peter, Richard, B., Constantine, G. Lyketsos, Malamon, John , Daniel, Chammiran , Martiniuk, Frank , Masliah, Eliezer , Wayne, C. McCormick, Susan, M, Andrew, Nesbit M, McDonough, Stefan, Ann., Canfield, Mesulam, Marsel, Bruce, L. Miller, Carol, A. Miller, Thomas, J. Montine, Amanda, J. Myers, John, M. Olichney, Joseph, E. Parisi, Peskind, Elaine R. , Pierce, Aimee, Wayne, W. Poon, Joseph, F. Quinn, Raj, Ashok , Raskind, Murray A. , Reisch, Joan, S., John, M. Ringman, Erik, D. Roberson, Howard, J. Rosen, Donald, R. Royall, Mark, A. Sager, Julie, A. Schneider, Lon, Su, William, W. Seeley, Small, Scott A. , Sonnen, Joshua, A., Robert, Aiko, Rudolph, E. Tanzi, Juan, Caballero, Debby, W. Tsuang, Vivianna, M. Van Deerlin, Badri, Nabeel, Harry, Vanessa, Vonsattel, Jean Paul, Weıntraub, Sandra , Kathleen, A Welsh-Bohmer, Kirk, C W, Thomas, SubinVarghese, Randall, Linnell B., Wu, Chuang‐Kuo, Steven, G. Younkin, Yu, Lei , Yu, Chang‐En , Graff‐Radford, Neill R. , Martinez, Izri, Ayodele, Temitope , Cantwell, Laura B., Jean‐Francois, Melissa, Kuzma, Amanda , Adams, Lonnie D., Chung, Jaeyoon , Jun, Gyungah , Hendrie, Hugh C. , Reiman, Eric M. , Kowall, Neil W. , Golde, Todd E. , Saykin, Andrew J. , Starks, Takiyah D. , Albert, Marilyn S. , Petersen, Ronald , Sano, Mary , Wısnıewskı, Thomas , Vassar, Robert , Kaye, Jeffrey A., Henderson, Victor W. , DeCarli, Charles , LaFerla, Frank M. , Brewer, James B., Miller, Bruce L. , Swerdlow, Russell H. , Paulson, Henry L. , Trojanowski, John Q. , Chui, Helena C., Rosenberg, Roger N., Craft, Suzanne , Grabowski, Thomas J. , Asthana, Sanjay , Morris, John C. , Strittmatter, Stephen M. , Kukull, Walter A. , Asthana, Sanjay , Jarvik, Gail P. , Cribbs, David H. , Sonnen, Joshua A. , Bennett, David A. , Saykin, Andrew J , Miller, Bruce L , Jarvik, Gail P , Paulson, Henry L , Hardy, John , Morris, John C , Goate, Alison M , Sonnen, Joshua , Barnes, Lisa L , Naj, Adam Christian , Hamilton‐Nelson, Kara L. , Manly, Jennifer J. , Kamboh, M. Ilyas , Farrer, Lindsay A. , Abner, Erin L. , Atwood, Craig, S., Becker, James, T., Eileen, H Bigio, Blacker, Deborah , Cao, Chuanhai , Cruchaga, Carlos , Dickson, Dennis, W., Duara, Ranjan , David, W. Fardo, Farlow, Martin, R., Ferris, Steven H. , Geschwind, Daniel, H., Ghetti, Bernardino , Gilbert, John, R., Håkonarson, Håkon , Honig, Lawrence, S., Huebinger, Ryan, M., Matthew, J Huentelman, Kauwe, John, S.K., Keene, C. Dirk , Kim, Ronald, Leung, Yuk Yee , Li, Ge , Lipton, Richard, B., Marson, Daniel, C., McDavid, Andrew, N., Mesulam, Marsel M. , Bruce, L Miller, Mukherjee, Shubhabrata , O’Bryant, Sid, E., Potter, Huntington , Qu, Liming , Raj, Ashok, Reisberg, Barry , Reisch, Joan, S., Rogaeva, Ekaterina A. , Julie, A Schneider, Schneider, Lon, S., William, W Seeley, Spina, Salvatore , George‐Hyslop, Peter St , Valladares, Otto , Vardarajan, Badri, N., Wilhelmsen, Kirk, C., Williamson, Jennifer , Wingo, Thomas, S., Woltjer, Randall, L., Steven, G Younkin, Zhao, Yi Chen , Logue, Mark W. , Adams, L.D., Vance, Jeffery M. , Cuccaro, Michael L. , Mez, Jesse , Lunetta, Kathryn L. , López, Oscar L. , Leverenz, James B. , Levey, Allan I. , Hyman, Bradley T. , Kaye, Jeffrey A., Eldik, Linda J. Van , Chui, Helena C.
JAMA Neurology | October 19, 2020 | Volume: 78 | Issue: 1 | Pages: 102
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.