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.
Convergent genetic and expression data implicate immunity in Alzheimer's disease
Jones, Lesley , Lambert, Jean‐Charles , Choi, Seung‐Hoan, Harold, Denise , Vedernikov, Alexey , Escott‐Price, Valentina , Stone, Timothy, Richards, Alexander , Bellenguez, Céline , Sims, Rebecca , DeStefano, Anita L. , Bis, Joshua C. , Beecham, Gary W. , Grenier‐Boley, Benjamin , Russo, Giancarlo , Thornton‐Wells, Tricia A., Jones, Nicola, Smith, Albert V. , Thomas, Charlene , Zélénika, Diana, Kamatani, Yoichiro, Lin, Chiao‐Feng , Schmidt, Helena , Kunkle, Brian W. , Dunstan, Melanie , Ruiz, Agustı́n , Bihoreau, Marie‐Thérèse, Reitz, Christiane, Hollingworth, Paul, Hanon, Olivier , Fitzpatrick, Annette L., Buxbaum, Joseph D. , Campion, Dominique , Crane, Paul K. , Guðnason, Vilmundur , Cruchaga, Carlos , Craig, David W. , Amin, Najaf , Jager, Philip L. De , Deramecourt, Vincent , Johnston, Janet, Evans, Denis A., Lovestone, Simon , Letteneur, Luc, Kornhuber, Johanes, Tárraga, Lluís , Eiriksdottir, Gudny, Goate, Alison , Fiévet, Nathalie, Huentelman, Matthew J. , Gill, Michael , Emilsson, Valur , Brown, Kristelle, Kamboh, M. Ilyas , Keller, Lina, Barberger‐Gateau, Pascale, McGuinness, Bernadette , Larson, Eric B., Dufouil, Carole , Todd, Stephen , Wallon, David , Kehoe, Patrick G. , George‐Hyslop, Peter St , Lleὀ, Alberti, Bayer, Anthony, Tsuang, Debby W. , Yu, Lei, Tsolaki, Magda , Bossù, Paola , Spalletta, Gianfranco , Proitsi, Petra, Collinge, John, Sorbi, Sandro , Hardy, John , Naranjo, María Cándida Déniz, Razquín, Cristina , Bosco, Paola , Clarke, Robert , Brayne, Carol , Galimberti, Daniela , CFAS, MRC, Moebus, Susanne , Mecocci, Patrizia , Zompo, Maria Del, Maier, Wolfgang, Hampel, Harald , Pilotto, Alberto, Bullido, María J. , Panza, Francesco , Caffarra, Paolo , Nacmias, Benedetta , Gilbert, John R., Mayhaus, Manuel, Jessen, Frank , Dichgans, Martin , Lannfelt, Lars , Håkonarson, Håkon , Pichler, Sabrina, Carrasquillo, Minerva M., Beekly, Duane, Alavarez, Victoria, Zou, Fanggeng, Younkin, Steven G., Hamilton‐Nelson, Kara L., Mateo, Ignacio, Faber, Kelley M., Jónsson, Pálmi V. , Combarros, Onofre, O‘Donovan, Michael , Cantwell, Laura B., Blacker, Deborah , Mead, Simon , Harris, Tamara B., Fratiglioni, Laura , Bruijn, Renée F.A.G. de, Passmore, Peter , Montine, Thomas J. , Bettens, Karolien, Rotter, Jerome I. , Brice, Alexis , Morgan, Kevin , Foroud, Tatiana, Kukull, Walter A. , Hannequin, Didier , Powell, John , Nalls, Michael A., Ritchie, Karen , Lunetta, Kathryn L. , Kauwe, John S.K., Boerwinkle, Eric , Riemenschneider, Matthias, Boada, Merçé , Hiltunen, Mikko , Martin, Eden R. , Pástor, Pau , Schmidt, Reinhold, Dartigues, Jean‐François, Mayeux, Richard , Tzourio, Christophe , Hofman, Albert , Nöthen, Markus M. , Graff, Caroline , Haines, Jonathan L. , Lathrop, Mark, Pericak‐Vance, Margaret A. , Launer, Lenore J. , Farrer, Lindsay A. , Duijn, Cornelia M. van , Broeckhoven, Christine Van , Ramı́rez, Alfredo , Schellenberg, Gerard D., Seshadri, Sudha , Amouyel, Philippe , Williams, Julie , Holmans, Peter , Bennett, David A. , Proitsi, Petroula , Ballantyne, Christie M. , Denning, Nicola , Wang, Weixin , Ibrahim‐Verbaas, Carla A. , Naj, Adam Christian , Gerrish, Amy , Jun, Gyungah , Chouraki, Vincent Antoine , Ikram, M. Arfan , Vardarajan, Badri Narayan , Kamatani, Yoichiro, Pasquier, Florence , Becker, Tim , Cruchaga, Carlos , Berr, Claudine , López, Oscar L. , Rubinsztein, David Chaim , Sleegers, Kristel , Myers, Amanda , Love, Seth , Rogaeva, Ekaterina A. , Gallacher, John , Clarimón, Jordi , Bayer, Anthony, Proitsi, Petra, Sánchez-García, Florentino , Fox, Nick C. , Mancuso, Michelangelo , CFAS, MRC, Carrasquillo, Minerva M. , Ingelsson, Martin , Valladares, Otto , Coto, Eliécer , Hamilton‐Nelson, Kara L. , Owen, Michael J. , Soininen, Hilkka S. , Mosley, Thomas H. , Bennett, David , Holmes, Clive , Riemenschneider, Matthias, Rujescu, Dan , Psaty, Bruce M. , Bennett, David A. , Dichgans, Martin , Ramirez, Alfredo , Hakonarson, Hakon , Nöthen, Markus M , Seshadri, Sudha , Hardy, John , Amouyel, Philippe , Tzourio, Christophe , van Duijn, Cornelia M , Smith, Albert V , Ballantyne, Christie M , Rotter, Jerome I , Moebus, Susanne , Ruiz, Agustín , Pastor, Pau , Boada, Merce , Tsolaki, Magda , Brice, Alexis , Goate, Alison M , Galimberti, Daniela , Escott-Price, Valentina , Mecocci, Patrizia , Nacmias, Benedetta , Graff, Caroline , Riemenschneider, Markus J.
Alzheimer's & Dementia | December 20, 2014 | Volume: 11 | Issue: 6 | Pages: 658-671
AbstractBackgroundLate‐onset Alzheimer's disease (AD) is heritable with 20 genes showing genome‐wide association in the International Genomics of Alzheimer's Project (IGAP). To identify the biology underlying the disease, we extended these genetic data in a pathway analysis.MethodsThe ALIGATOR and GSEA algorithms were used in the IGAP data to identify associated functional pathways and correlated gene expression networks in human brain.ResultsALIGATOR identified an excess of curated biological pathways showing enrichment of association. Enriched areas of biology included the immune response (P = 3.27 × 10−12 after multiple testing correction for pathways), regulation of endocytosis (P = 1.31 × 10−11), cholesterol transport (P = 2.96 × 10−9), and proteasome‐ubiquitin activity (P = 1.34 × 10−6). Correlated gene expression analysis identified four significant network modules, all related to the immune response (corrected P = .002–.05).ConclusionsThe immune response, regulation of endocytosis, cholesterol transport, and protein ubiquitination represent prime targets for AD therapeutics.
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
Susceptibility Locus for Alzheimer's Disease on Chromosome 10
Holmans, Peter , Marshall, Helen, Kwon, Jennifer M. , Meyer, David , Ramic, Dzanan, Shears, Shantia, DeVriéze, Fabienne Wavrant, Hamshere, Marian L. , Abraham, Richard, Tunstall, Nigel, Rice, Frances , Carty, Stephanie, Lillystone, Sara, Kehoe, Patrick G. , Rudrasingham, Varuni, Jones, Lesley , Lovestone, Simon , Pérez‐Tur, Jordi , Williams, Julie , Hardy, John , Goate, Alison , Myers, Amanda , Booth, Jeremy , Crook, Richard , Owen, Michael J. , Hardy, John , Goate, Alison M
Science | July 27, 2002 | Volume: 290 | Issue: 5500 | Pages: 2304-2305
The apolipoprotein E ( APOE ) gene is the only genetic risk factor that has so far been linked to risk for late-onset Alzheimer's disease (LOAD). However, 50 percent of Alzheimer's disease cases do not carry an APOE4 allele, suggesting that other risk factors must exist. We performed a two-stage genome-wide screen in sibling pairs with LOAD to detect other susceptibility loci. Here we report evidence for an Alzheimer's disease locus on chromosome 10. Our stage one multipoint lod score (logarithm of the odds ratio for linkage/no linkage) of 2.48 (266 sibling pairs) increased to 3.83 in stage 2 (429 sibling pairs) close to D10S1225 (79 centimorgans). This locus modifies risk for Alzheimer's disease independent of APOE genotype.