784 results on '"Beecham, Gary W"'
Search Results
202. Fine‐mapping of chromosome 9p21 linkage in Puerto Rican Alzheimer disease families.
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Celis, Katrina, Rajabli, Farid, Simon, Shaina A, Wang, Liyong, Hamilton‐Nelson, Kara L., Adams, Larry D., Mena, Pedro Ramon, Whitehead, Patrice L., Van Booven, Derek, Feliciano‐Astacio, Briseida E., Chinea, Angel, Feliciano, Nereida I, Acosta, Heriberto, Dalgard, Clifton L., Haines, Jonathan L., Vance, Jeffery M., Cuccaro, Michael L., Beecham, Gary W., Dykxhoorn, Derek M., and Griswold, Anthony J.
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- 2022
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203. The Relationship of Alzheimer's Disease, Stroke and Ancestry in the Puerto Rican Alzheimer Disease Population.
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Feliciano‐Astacio, Briseida E., Beecham, Gary W., Hamilton‐Nelson, Kara L., Silva‐Vergara, Concepcion, Contreras, Maricarmen, Mena, Pedro Ramon, Adams, Larry D., Acosta, Heriberto, Feliciano, Nereida I, Lopez, Alexandra, Cuccaro, Michael L., Vance, Jeffery M., and Pericak‐Vance, Margaret A.
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- 2022
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204. Novel late-onset Alzheimer disease loci variants associate with brain gene expression
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Allen, Mariet, Zou, Fanggeng, Chai, High Seng, Younkin, Curtis S, Crook, Julia, Pankratz, V Shane, Carrasquillo, Minerva M, Rowley, Christopher N, Nair, Asha A, Middha, Sumit, Maharjan, Sooraj, Nguyen, Thuy, Ma, Li, Malphrus, Kimberly G, Palusak, Ryan, Lincoln, Sarah, Bisceglio, Gina, Georgescu, Constantin, Schultz, Debra, Rakhshan, Fariborz, Kolbert, Christopher P, Jen, Jin, Haines, Jonathan L, Mayeux, Richard, Pericak-Vance, Margaret A, Farrer, Lindsay A, Schellenberg, Gerard D, Petersen, Ronald C, Graff-Radford, Neill R, Dickson, Dennis W, Younkin, Steven G, Ertekin-Taner, Nilüfer, Alzheimer's Disease Genetics Consortium (ADGC), Apostolova, Liana G, Arnold, Steven E, Baldwin, Clinton T, Barber, Robert, Barmada, Michael M, Beach, Thomas, Beecham, Gary W, Beekly, Duane, Bennett, David A, Bigio, Eileen H, Bird, Thomas D, Blacker, Deborah, Boeve, Bradley F, Bowen, James D, Boxer, Adam, Burke, James R, Buros, Jacqueline, Buxbaum, Joseph D, Cairns, Nigel J, Cantwell, Laura B, Cao, Chuanhai, Carlson, Chris S, Carney, Regina M, Carroll, Steven L, Chui, Helena C, Clark, David G, Corneveaux, Jason, Cotman, Carl W, Crane, Paul K, Cruchaga, Carlos, Cummings, Jeffrey L, De Jager, Philip L, DeCarli, Charles, DeKosky, Steven T, Demirci, F Yesim, Diaz-Arrastia, Ramon, Dick, Malcolm, Dombroski, Beth A, Duara, Ranjan, Ellis, William D, Evans, Denis, Faber, Kelley M, Fallon, Kenneth B, Farlow, Martin R, Ferris, Steven, Foroud, Tatiana M, Frosch, Matthew, Galasko, Douglas R, Gallins, Paul J, Ganguli, Mary, Gearing, Marla, Geschwind, Daniel H, Ghetti, Bernardino, Gilbert, John R, Gilman, Sid, Giordani, Bruno, Glass, Jonathan D, Goate, Alison M, Green, Robert C, Growdon, John H, Hakonarson, Hakon, Hamilton, Ronald L, Hardy, John, Harrell, Lindy E, Head, Elizabeth, Honig, Lawrence S, and Huentelman, Matthew J
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Male ,Aging ,Genotype ,Apolipoprotein E4 ,Clinical Sciences ,Gene Dosage ,Gene Expression ,Neurodegenerative ,Alzheimer's Disease ,Alzheimer Disease ,Risk Factors ,Clinical Research ,Acquired Cognitive Impairment ,Genetics ,Humans ,2.1 Biological and endogenous factors ,Genetic Predisposition to Disease ,Polymorphism ,Aetiology ,Alleles ,Aged ,Brain Chemistry ,Neurology & Neurosurgery ,Human Genome ,Neurosciences ,Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD) ,Single Nucleotide ,Temporal Lobe ,Brain Disorders ,Neurological ,Alzheimer's Disease Genetics Consortium ,Linear Models ,RNA ,Female ,Dementia ,Cognitive Sciences ,Autopsy - Abstract
ObjectiveRecent genome-wide association studies (GWAS) of late-onset Alzheimer disease (LOAD) identified 9 novel risk loci. Discovery of functional variants within genes at these loci is required to confirm their role in Alzheimer disease (AD). Single nucleotide polymorphisms that influence gene expression (eSNPs) constitute an important class of functional variants. We therefore investigated the influence of the novel LOAD risk loci on human brain gene expression.MethodsWe measured gene expression levels in the cerebellum and temporal cortex of autopsied AD subjects and those with other brain pathologies (∼400 total subjects). To determine whether any of the novel LOAD risk variants are eSNPs, we tested their cis-association with expression of 6 nearby LOAD candidate genes detectable in human brain (ABCA7, BIN1, CLU, MS4A4A, MS4A6A, PICALM) and an additional 13 genes ±100 kb of these SNPs. To identify additional eSNPs that influence brain gene expression levels of the novel candidate LOAD genes, we identified SNPs ±100 kb of their location and tested for cis-associations.ResultsCLU rs11136000 (p = 7.81 × 10(-4)) and MS4A4A rs2304933/rs2304935 (p = 1.48 × 10(-4)-1.86 × 10(-4)) significantly influence temporal cortex expression levels of these genes. The LOAD-protective CLU and risky MS4A4A locus alleles associate with higher brain levels of these genes. There are other cis-variants that significantly influence brain expression of CLU and ABCA7 (p = 4.01 × 10(-5)-9.09 × 10(-9)), some of which also associate with AD risk (p = 2.64 × 10(-2)-6.25 × 10(-5)).ConclusionsCLU and MS4A4A eSNPs may at least partly explain the LOAD risk association at these loci. CLU and ABCA7 may harbor additional strong eSNPs. These results have implications in the search for functional variants at the novel LOAD risk loci.
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- 2012
205. Confidence Interval of the Likelihood Ratio Associated with Mixed Stain DNA Evidence*
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Beecham, Gary W. and Weir, Bruce S.
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Likelihood Functions ,Gene Frequency ,Confidence Intervals ,Humans ,DNA ,Databases, Nucleic Acid ,DNA Fingerprinting ,Article - Abstract
Likelihood ratios are necessary to properly interpret mixed stain DNA evidence. They can flexibly consider alternate hypotheses and can account for population substructure. The likelihood ratio should be seen as an estimate and not a fixed value, because the calculations are functions of allelic frequency estimates that were estimated from a small portion of the population. Current methods do not account for uncertainty in the likelihood ratio estimates and are therefore an incomplete picture of the strength of the evidence. We propose the use of a confidence interval to report the consequent variation of likelihood ratios. The confidence interval is calculated using the standard forensic likelihood ratio formulae and a variance estimate derived using the Taylor expansion. The formula is explained, and a computer program has been made available. Numeric work shows that the evidential strength of DNA profiles decreases as the variation among populations increases.
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- 2010
206. Genome‐wide linkage analyses of non‐Hispanic white families identify novel loci for familial late‐onset Alzheimer's disease
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Kunkle, Brian W., primary, Jaworski, James, additional, Barral, Sandra, additional, Vardarajan, Badri, additional, Beecham, Gary W., additional, Martin, Eden R., additional, Cantwell, Laura S., additional, Partch, Amanda, additional, Bird, Thomas D., additional, Raskind, Wendy H., additional, DeStefano, Anita L., additional, Carney, Regina M., additional, Cuccaro, Michael, additional, Vance, Jeffrey M., additional, Farrer, Lindsay A., additional, Goate, Alison M., additional, Foroud, Tatiana, additional, Mayeux, Richard P., additional, Schellenberg, Gerard D., additional, Haines, Jonathan L., additional, and Pericak‐Vance, Margaret A., additional
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- 2015
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207. O3-13-02: Whole-exome sequencing in early-onset Alzheimer disease cases identifies novel candidate genes
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Beecham, Gary W., primary, Kunkle, Brian W., additional, Vardarajan, Badri, additional, Whitehead, Patrice L., additional, Rolati, Sophie, additional, Martin, Eden R., additional, Gilbert, John R., additional, Mayeux, Richard, additional, Haines, Jonathan L., additional, and Pericak-Vance, Margaret A., additional
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- 2015
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208. Rarity of the Alzheimer Disease–ProtectiveAPPA673T Variant in the United States
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Wang, Li-San, primary, Naj, Adam C., additional, Graham, Robert R., additional, Crane, Paul K., additional, Kunkle, Brian W., additional, Cruchaga, Carlos, additional, Murcia, Josue D. Gonzalez, additional, Cannon-Albright, Lisa, additional, Baldwin, Clinton T., additional, Zetterberg, Henrik, additional, Blennow, Kaj, additional, Kukull, Walter A., additional, Faber, Kelley M., additional, Schupf, Nicole, additional, Norton, Maria C., additional, Tschanz, JoAnn T., additional, Munger, Ronald G., additional, Corcoran, Christopher D., additional, Rogaeva, Ekaterina, additional, Lin, Chiao-Feng, additional, Dombroski, Beth A., additional, Cantwell, Laura B., additional, Partch, Amanda, additional, Valladares, Otto, additional, Hakonarson, Hakon, additional, St George-Hyslop, Peter, additional, Green, Robert C., additional, Goate, Alison M., additional, Foroud, Tatiana M., additional, Carney, Regina M., additional, Larson, Eric B., additional, Behrens, Timothy W., additional, Kauwe, John S. K., additional, Haines, Jonathan L., additional, Farrer, Lindsay A., additional, Pericak-Vance, Margaret A., additional, Mayeux, Richard, additional, Schellenberg, Gerard D., additional, Albert, Marilyn S., additional, Albin, Roger L., additional, Apostolova, Liana G., additional, Arnold, Steven E., additional, Barber, Robert, additional, Barmada, M. Michael, additional, Barnes, Lisa L., additional, Beach, Thomas G., additional, Becker, James T., additional, Beecham, Gary W., additional, Beekly, Duane, additional, Bennett, David A., additional, Bigio, Eileen H., additional, Bird, Thomas D., additional, Blacker, Deborah, additional, Boeve, Bradley F., additional, Bowen, James D., additional, Boxer, Adam, additional, Burke, James R., additional, Buxbaum, Joseph D., additional, Cairns, Nigel J., additional, Cao, Chuanhai, additional, Carlson, Chris S., additional, Carroll, Steven L., additional, Chui, Helena C., additional, Clark, David G., additional, Cribbs, David H., additional, Crocco, Elizabeth A., additional, DeCarli, Charles, additional, DeKosky, Steven T., additional, Demirci, F. Yesim, additional, Dick, Malcolm, additional, Dickson, Dennis W., additional, Duara, Ranjan, additional, Ertekin-Taner, Nilufer, additional, Fallon, Kenneth B., additional, Farlow, Martin R., additional, Ferris, Steven, additional, Frosch, Matthew P., additional, Galasko, Douglas R., additional, Ganguli, Mary, additional, Gearing, Marla, additional, Geschwind, Daniel H., additional, Ghetti, Bernardino, additional, Gilbert, John R., additional, Glass, Jonathan D., additional, Graff-Radford, Neill R., additional, Growdon, John H., additional, Hamilton, Ronald L., additional, Hamilton-Nelson, Kara L., additional, Harrell, Lindy E., additional, Head, Elizabeth, additional, Honig, Lawrence S., additional, Hulette, Christine M., additional, Hyman, Bradley T., additional, Jarvik, Gail P., additional, Jicha, Gregory A., additional, Jin, Lee-Way, additional, Jun, Gyungah, additional, Kamboh, M. Ilyas, additional, Karydas, Anna, additional, Kaye, Jeffrey A., additional, Kim, Ronald, additional, Koo, Edward H., additional, Kowall, Neil W., additional, Kramer, Joel H., additional, Kramer, Patricia, additional, LaFerla, Frank M., additional, Lah, James J., additional, Leverenz, James B., additional, Levey, Allan I., additional, Li, Ge, additional, Lieberman, Andrew P., additional, Lopez, Oscar L., additional, Lunetta, Kathryn L., additional, Lyketsos, Constantine G., additional, Mack, Wendy J., additional, Marson, Daniel C., additional, Martin, Eden R., additional, Martiniuk, Frank, additional, Mash, Deborah C., additional, Masliah, Eliezer, additional, McCormick, Wayne C., additional, McCurry, Susan M., additional, McDavid, Andrew N., additional, McKee, Ann C., additional, Mesulam, M. Marsel, additional, Miller, Bruce L., additional, Miller, Carol A., additional, Miller, Joshua W., additional, Montine, Thomas J., additional, Morris, John C., additional, Murrell, Jill R., additional, Olichney, John M., additional, Parisi, Joseph E., additional, Perry, William, additional, Peskind, Elaine, additional, Petersen, Ronald C., additional, Pierce, Aimee, additional, Poon, Wayne W., additional, Potter, Huntington, additional, Quinn, Joseph F., additional, Raj, Ashok, additional, Raskind, Murray, additional, Reiman, Eric M., additional, Reisberg, Barry, additional, Reitz, Christiane, additional, Ringman, John M., additional, Roberson, Erik D., additional, Rosen, Howard J., additional, Rosenberg, Roger N., additional, Sano, Mary, additional, Saykin, Andrew J., additional, Schneider, Julie A., additional, Schneider, Lon S., additional, Seeley, William W., additional, Smith, Amanda G., additional, Sonnen, Joshua A., additional, Spina, Salvatore, additional, Stern, Robert A., additional, Tanzi, Rudolph E., additional, Thornton-Wells, Tricia A., additional, Trojanowski, John Q., additional, Troncoso, Juan C., additional, Tsuang, Debby W., additional, Van Deerlin, Vivianna M., additional, Van Eldik, Linda J., additional, Vardarajan, Badri N., additional, Vinters, Harry V., additional, Vonsattel, Jean Paul, additional, Weintraub, Sandra, additional, Welsh-Bohmer, Kathleen A., additional, Williamson, Jennifer, additional, Wishnek, Sarah, additional, Woltjer, Randall L., additional, Wright, Clinton B., additional, Younkin, Steven G., additional, Yu, Chang-En, additional, and Yu, Lei, additional
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- 2015
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209. Effects of Multiple Genetic Loci on Age at Onset in Late-Onset Alzheimer Disease
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Naj, Adam C, Naj, Adam C, Jun, Gyungah, Reitz, Christiane, Kunkle, Brian W, Perry, William, Park, Yo Son, Beecham, Gary W, Rajbhandary, Ruchita A, Hamilton-Nelson, Kara L, Wang, Li-San, Kauwe, John S. K, Huentelman, Matthew J, Myers, Amanda J, Bird, Thomas D, Boeve, Bradley F, Baldwin, Clinton T, Jarvik, Gail P, Crane, Paul K, Rogaeva, Ekaterina, Barmada, M. Michael, Demirci, F. Yesim, Cruchaga, Carlos, Kramer, Patricia L, Ertekin-Taner, Nilufer, Hardy, John, Graff-Radford, Neill R, Green, Robert C, Larson, Eric B, St. George-Hyslop, Peter H, Buxbaum, Joseph D, Evans, Denis A, Schneider, Julie A, Lunetta, Kathryn L, Kamboh, M. Ilyas, Saykin, Andrew J, Reiman, Eric M, De Jager, Philip L, Bennett, David A, Morris, John C, Montine, Thomas J, Goate, Alison M, Blacker, Deborah, Tsuang, Debby W, Hakonarson, Hakon, Kukull, Walter A, Foroud, Tatiana M, Martin, Eden R, Haines, Jonathan L, Mayeux, Richard P, Farrer, Lindsay A, Schellenberg, Gerard D, Pericak-Vance, Margaret A, Albert, Marilyn S, Albin, Roger L, Apostolova, Liana G, Arnold, Steven E, Barber, Robert, Barnes, Lisa L, Beach, Thomas G, Becker, James T, Beekly, Duane, Bigio, Eileen H, Bowen, James D, Boxer, Adam, Burke, James R, Cairns, Nigel J, Cantwell, Laura B, Cao, Chuanhai, Carlson, Chris S, Carney, Regina M, Carrasquillo, Minerva M, Carroll, Steven L, Chui, Helena C, Clark, David G, Corneveaux, Jason, Cribbs, David H, Crocco, Elizabeth A, DeCarli, Charles, DeKosky, Steven T, Dick, Malcolm, Dickson, Dennis W, Duara, Ranjan, Faber, Kelley M, Fallon, Kenneth B, Farlow, Martin R, Ferris, Steven, Frosch, Matthew P, Galasko, Douglas R, Ganguli, Mary, Gearing, Marla, Geschwind, Daniel H, Ghetti, Bernardino, Gilbert, John R, Glass, Jonathan D, Growdon, John H, Hamilton, Ronald L, Harrell, Lindy E, Head, Elizabeth, Honig, Lawrence S, Hulette, Christine M, Naj, Adam C, Naj, Adam C, Jun, Gyungah, Reitz, Christiane, Kunkle, Brian W, Perry, William, Park, Yo Son, Beecham, Gary W, Rajbhandary, Ruchita A, Hamilton-Nelson, Kara L, Wang, Li-San, Kauwe, John S. K, Huentelman, Matthew J, Myers, Amanda J, Bird, Thomas D, Boeve, Bradley F, Baldwin, Clinton T, Jarvik, Gail P, Crane, Paul K, Rogaeva, Ekaterina, Barmada, M. Michael, Demirci, F. Yesim, Cruchaga, Carlos, Kramer, Patricia L, Ertekin-Taner, Nilufer, Hardy, John, Graff-Radford, Neill R, Green, Robert C, Larson, Eric B, St. George-Hyslop, Peter H, Buxbaum, Joseph D, Evans, Denis A, Schneider, Julie A, Lunetta, Kathryn L, Kamboh, M. Ilyas, Saykin, Andrew J, Reiman, Eric M, De Jager, Philip L, Bennett, David A, Morris, John C, Montine, Thomas J, Goate, Alison M, Blacker, Deborah, Tsuang, Debby W, Hakonarson, Hakon, Kukull, Walter A, Foroud, Tatiana M, Martin, Eden R, Haines, Jonathan L, Mayeux, Richard P, Farrer, Lindsay A, Schellenberg, Gerard D, Pericak-Vance, Margaret A, Albert, Marilyn S, Albin, Roger L, Apostolova, Liana G, Arnold, Steven E, Barber, Robert, Barnes, Lisa L, Beach, Thomas G, Becker, James T, Beekly, Duane, Bigio, Eileen H, Bowen, James D, Boxer, Adam, Burke, James R, Cairns, Nigel J, Cantwell, Laura B, Cao, Chuanhai, Carlson, Chris S, Carney, Regina M, Carrasquillo, Minerva M, Carroll, Steven L, Chui, Helena C, Clark, David G, Corneveaux, Jason, Cribbs, David H, Crocco, Elizabeth A, DeCarli, Charles, DeKosky, Steven T, Dick, Malcolm, Dickson, Dennis W, Duara, Ranjan, Faber, Kelley M, Fallon, Kenneth B, Farlow, Martin R, Ferris, Steven, Frosch, Matthew P, Galasko, Douglas R, Ganguli, Mary, Gearing, Marla, Geschwind, Daniel H, Ghetti, Bernardino, Gilbert, John R, Glass, Jonathan D, Growdon, John H, Hamilton, Ronald L, Harrell, Lindy E, Head, Elizabeth, Honig, Lawrence S, and Hulette, Christine M
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- 2014
210. Gene-wide analysis detects two new susceptibility genes for Alzheimer's disease.
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Luxembourg Centre for Systems Biomedicine (LCSB): Bioinformatics Core (R. Schneider Group) [research center], Escott-Price, Valentina, Bellenguez, Celine, Wang, Li-San, Choi, Seung-Hoan, Harold, Denise, Jones, Lesley, Holmans, Peter, Gerrish, Amy, Vedernikov, Alexey, Richards, Alexander, DeStefano, Anita L., Lambert, Jean-Charles, Ibrahim-Verbaas, Carla A., Naj, Adam C., Sims, Rebecca, Jun, Gyungah, Bis, Joshua C., Beecham, Gary W., Grenier-Boley, Benjamin, Russo, Giancarlo, Thornton-Wells, Tricia A., Denning, Nicola, Smith, Albert V., Chouraki, Vincent, Thomas, Charlene, Ikram, M. Arfan, Zelenika, Diana, Vardarajan, Badri N., Kamatani, Yoichiro, Lin, Chiao-Feng, Schmidt, Helena, Kunkle, Brian, Dunstan, Melanie L., Vronskaya, Maria, Johnson, Andrew D., Ruiz, Agustin, Bihoreau, Marie-Therese, Reitz, Christiane, Pasquier, Florence, Hollingworth, Paul, Hanon, Olivier, Fitzpatrick, Annette L., Buxbaum, Joseph D., Campion, Dominique, Crane, Paul K., Baldwin, Clinton, Becker, Tim, Gudnason, Vilmundur, Cruchaga, Carlos, Craig, David, Amin, Najaf, Berr, Claudine, Lopez, Oscar L., De Jager, Philip L., Deramecourt, Vincent, Johnston, Janet A., Evans, Denis, Lovestone, Simon, Letenneur, Luc, Hernandez, Isabel, Rubinsztein, David C., Eiriksdottir, Gudny, Sleegers, Kristel, Goate, Alison M., Fievet, Nathalie, Huentelman, Matthew J., Gill, Michael, Brown, Kristelle, Kamboh, M. Ilyas, Keller, Lina, Barberger-Gateau, Pascale, McGuinness, Bernadette, Larson, Eric B., Myers, Amanda J., Dufouil, Carole, Todd, Stephen, Wallon, David, Love, Seth, Rogaeva, Ekaterina, Gallacher, John, George-Hyslop, Peter St, Clarimon, Jordi, Lleo, Alberto, Bayer, Anthony, Tsuang, Debby W., Yu, Lei, Tsolaki, Magda, Bossu, Paola, Spalletta, Gianfranco, Proitsi, Petra, Collinge, John, Sorbi, Sandro, Garcia, Florentino Sanchez, Fox, Nick C., Hardy, John, Naranjo, Maria Candida Deniz, Bosco, Paolo, Clarke, Robert, Brayne, Carol, Galimberti, Daniela, Scarpini, Elio, Bonuccelli, Ubaldo, Mancuso, Michelangelo, Siciliano, Gabriele, Moebus, Susanne, Mecocci, Patrizia, Zompo, Maria Del, Maier, Wolfgang, Hampel, Harald, Pilotto, Alberto, Frank-Garcia, Ana, Panza, Francesco, Solfrizzi, Vincenzo, Caffarra, Paolo, Nacmias, Benedetta, Perry, William, Mayhaus, Manuel, Lannfelt, Lars, Hakonarson, Hakon, Pichler, Sabrina, Carrasquillo, Minerva M., Ingelsson, Martin, Beekly, Duane, Alvarez, Victoria, Zou, Fanggeng, Valladares, Otto, Younkin, Steven G., Coto, Eliecer, Hamilton-Nelson, Kara L., Gu, Wei, Razquin, Cristina, Pastor, Pau, Mateo, Ignacio, Owen, Michael J., Faber, Kelley M., Jonsson, Palmi V., Combarros, Onofre, O'Donovan, Michael C., Cantwell, Laura B., Soininen, Hilkka, Blacker, Deborah, Mead, Simon, Mosley, Thomas H. Jr, Bennett, David A., Harris, Tamara B., Fratiglioni, Laura, Holmes, Clive, de Bruijn, Renee F. A. G., Passmore, Peter, Montine, Thomas J., Bettens, Karolien, Rotter, Jerome I., Brice, Alexis, Morgan, Kevin, Foroud, Tatiana M., Kukull, Walter A., Hannequin, Didier, Powell, John F., Nalls, Michael A., Ritchie, Karen, Lunetta, Kathryn L., Kauwe, John S. K., Boerwinkle, Eric, Riemenschneider, Matthias, Boada, Merce, Hiltunen, Mikko, Martin, Eden R., Schmidt, Reinhold, Rujescu, Dan, Dartigues, Jean-Francois, Mayeux, Richard, Tzourio, Christophe, Hofman, Albert, Nothen, Markus M., Graff, Caroline, Psaty, Bruce M., Haines, Jonathan L., Lathrop, Mark, Pericak-Vance, Margaret A., Launer, Lenore J., Van Broeckhoven, Christine, Farrer, Lindsay A., van Duijn, Cornelia M., Ramirez, Alfredo, Seshadri, Sudha, Schellenberg, Gerard D., Amouyel, Philippe, Williams, Julie, Luxembourg Centre for Systems Biomedicine (LCSB): Bioinformatics Core (R. Schneider Group) [research center], Escott-Price, Valentina, Bellenguez, Celine, Wang, Li-San, Choi, Seung-Hoan, Harold, Denise, Jones, Lesley, Holmans, Peter, Gerrish, Amy, Vedernikov, Alexey, Richards, Alexander, DeStefano, Anita L., Lambert, Jean-Charles, Ibrahim-Verbaas, Carla A., Naj, Adam C., Sims, Rebecca, Jun, Gyungah, Bis, Joshua C., Beecham, Gary W., Grenier-Boley, Benjamin, Russo, Giancarlo, Thornton-Wells, Tricia A., Denning, Nicola, Smith, Albert V., Chouraki, Vincent, Thomas, Charlene, Ikram, M. Arfan, Zelenika, Diana, Vardarajan, Badri N., Kamatani, Yoichiro, Lin, Chiao-Feng, Schmidt, Helena, Kunkle, Brian, Dunstan, Melanie L., Vronskaya, Maria, Johnson, Andrew D., Ruiz, Agustin, Bihoreau, Marie-Therese, Reitz, Christiane, Pasquier, Florence, Hollingworth, Paul, Hanon, Olivier, Fitzpatrick, Annette L., Buxbaum, Joseph D., Campion, Dominique, Crane, Paul K., Baldwin, Clinton, Becker, Tim, Gudnason, Vilmundur, Cruchaga, Carlos, Craig, David, Amin, Najaf, Berr, Claudine, Lopez, Oscar L., De Jager, Philip L., Deramecourt, Vincent, Johnston, Janet A., Evans, Denis, Lovestone, Simon, Letenneur, Luc, Hernandez, Isabel, Rubinsztein, David C., Eiriksdottir, Gudny, Sleegers, Kristel, Goate, Alison M., Fievet, Nathalie, Huentelman, Matthew J., Gill, Michael, Brown, Kristelle, Kamboh, M. Ilyas, Keller, Lina, Barberger-Gateau, Pascale, McGuinness, Bernadette, Larson, Eric B., Myers, Amanda J., Dufouil, Carole, Todd, Stephen, Wallon, David, Love, Seth, Rogaeva, Ekaterina, Gallacher, John, George-Hyslop, Peter St, Clarimon, Jordi, Lleo, Alberto, Bayer, Anthony, Tsuang, Debby W., Yu, Lei, Tsolaki, Magda, Bossu, Paola, Spalletta, Gianfranco, Proitsi, Petra, Collinge, John, Sorbi, Sandro, Garcia, Florentino Sanchez, Fox, Nick C., Hardy, John, Naranjo, Maria Candida Deniz, Bosco, Paolo, Clarke, Robert, Brayne, Carol, Galimberti, Daniela, Scarpini, Elio, Bonuccelli, Ubaldo, Mancuso, Michelangelo, Siciliano, Gabriele, Moebus, Susanne, Mecocci, Patrizia, Zompo, Maria Del, Maier, Wolfgang, Hampel, Harald, Pilotto, Alberto, Frank-Garcia, Ana, Panza, Francesco, Solfrizzi, Vincenzo, Caffarra, Paolo, Nacmias, Benedetta, Perry, William, Mayhaus, Manuel, Lannfelt, Lars, Hakonarson, Hakon, Pichler, Sabrina, Carrasquillo, Minerva M., Ingelsson, Martin, Beekly, Duane, Alvarez, Victoria, Zou, Fanggeng, Valladares, Otto, Younkin, Steven G., Coto, Eliecer, Hamilton-Nelson, Kara L., Gu, Wei, Razquin, Cristina, Pastor, Pau, Mateo, Ignacio, Owen, Michael J., Faber, Kelley M., Jonsson, Palmi V., Combarros, Onofre, O'Donovan, Michael C., Cantwell, Laura B., Soininen, Hilkka, Blacker, Deborah, Mead, Simon, Mosley, Thomas H. Jr, Bennett, David A., Harris, Tamara B., Fratiglioni, Laura, Holmes, Clive, de Bruijn, Renee F. A. G., Passmore, Peter, Montine, Thomas J., Bettens, Karolien, Rotter, Jerome I., Brice, Alexis, Morgan, Kevin, Foroud, Tatiana M., Kukull, Walter A., Hannequin, Didier, Powell, John F., Nalls, Michael A., Ritchie, Karen, Lunetta, Kathryn L., Kauwe, John S. K., Boerwinkle, Eric, Riemenschneider, Matthias, Boada, Merce, Hiltunen, Mikko, Martin, Eden R., Schmidt, Reinhold, Rujescu, Dan, Dartigues, Jean-Francois, Mayeux, Richard, Tzourio, Christophe, Hofman, Albert, Nothen, Markus M., Graff, Caroline, Psaty, Bruce M., Haines, Jonathan L., Lathrop, Mark, Pericak-Vance, Margaret A., Launer, Lenore J., Van Broeckhoven, Christine, Farrer, Lindsay A., van Duijn, Cornelia M., Ramirez, Alfredo, Seshadri, Sudha, Schellenberg, Gerard D., Amouyel, Philippe, and Williams, Julie
- Abstract
BACKGROUND: Alzheimer's disease is a common debilitating dementia with known heritability, for which 20 late onset susceptibility loci have been identified, but more remain to be discovered. This study sought to identify new susceptibility genes, using an alternative gene-wide analytical approach which tests for patterns of association within genes, in the powerful genome-wide association dataset of the International Genomics of Alzheimer's Project Consortium, comprising over 7 m genotypes from 25,580 Alzheimer's cases and 48,466 controls. PRINCIPAL FINDINGS: In addition to earlier reported genes, we detected genome-wide significant loci on chromosomes 8 (TP53INP1, p = 1.4x10-6) and 14 (IGHV1-67 p = 7.9x10-8) which indexed novel susceptibility loci. SIGNIFICANCE: The additional genes identified in this study, have an array of functions previously implicated in Alzheimer's disease, including aspects of energy metabolism, protein degradation and the immune system and add further weight to these pathways as potential therapeutic targets in Alzheimer's disease.
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- 2014
211. RESOURCE OF MULTIPLEX AFRICAN AMERICAN FAMILIES FOR WHOLE-GENOME SEQUENCING
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Cuccaro, Michael L., Reitz, Christiane, Beecham, Gary W., Cukier, Holly N., Celis, Katrina, Adams, Larry Deon, Starks, Takiyah, Joseph, Nancy, Whitehead, Patrice L., Hamilton-Nelson, Kara L., Reyes-Dumeyer, Dolly, Byfield, Grace, Bennett, David A., Rosenberg, Roger N., Boeve, Bradley F., Sweet, Robert A., Cruchaga, Carlos, Haines, Jonathan L., Vance, Jeffery M., Byrd, Goldie S., Mayeux, Richard, and Pericak-Vance, Margaret A.
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- 2017
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212. THE PUERTO RICAN ALZHEIMER DISEASE INITIATIVE (PRADI): INITIAL CLINICAL FINDINGS
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Celis, Katrina, Feliciano-Astacio, Briseida E., Adams, Larry Deon, Bussies, Parker, Sierra, Carolina, Hamilton-Nelson, Kara L., Rajabli, Farid, Acosta, Heriberto, Chinea, Angel, McCauley, Jacob L., Vance, Jeffery M., Cuccaro, Michael L., Beecham, Gary W., and Pericak-Vance, Margaret A.
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- 2017
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213. THE RELEVANCE OF APOE4 TO ALZHEIMER’S DISEASE IN THE PRESENCE OF LOCAL ANCESTRY DIFFERENCES
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Rajabli, Farid, Hamilton-Nelson, Kara L., Feliciano-Astacio, Briseida E., Celis, Katrina, Adams, Larry Deon, Bussies, Parker, Sierra, Carolina, Chinea, Angel, Acosta, Heriberto, McCauley, Jacob L., Vance, Jeffery M., Cuccaro, Michael L., Haines, Jonathan L., Bush, William S., Beecham, Gary W., and Pericak-Vance, Margaret A.
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- 2017
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214. COLLECTION OF MULTIPLEX FAMILIES WITH UNEXPLAINED EARLY-ONSET ALZHEIMER’S DISEASE FOR GENOMIC RESEARCH
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Reitz, Christiane, Tang, Min, Reyes-Dumeyer, Dolly, Kunkle, Brian W., Hamilton-Nelson, Kara L., Lantigua, Rafael, Medrano, Martin, Martin, Eden R., Jimenez-Velazquez, Ivonne Z., Pericak-Vance, Margaret A., Mayeux, Richard, and Beecham, Gary W.
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- 2017
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215. THE PUERTO RICO ALZHEIMER DISEASE INITIATIVE (PRADI): A MULTISOURCE ASCERTAINMENT APPROACH
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Feliciano-Astacio, Briseida E., Celis, Katrina, Adams, Larry Deon, Hamilton-Nelson, Kara L., Bussies, Parker, Sierra, Carolina, Feliciano, Nereida, Chinea, Angel, Acosta, Heriberto, McCauley, Jacob L., Vance, Jeffery M., Cuccaro, Michael L., Beecham, Gary W., and Pericak-Vance, Margaret A.
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- 2017
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216. INFLUENCE OF COMMUNITY ENGAGED FAMILY CONNECTOR IN RECRUITING AND ASCERTAINING AFRICAN AMERICANS’ FAMILY MEMBERS FOR GENOMIC RESEARCH
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Byfield, Grace, Starks, Takiyah, Byrd, Goldie S., Cuccaro, Michael L., Adams, Larry Deon, Whitehead, Patrice L., Reitz, Christiane, Beecham, Gary W., Reyes-Dumeyer, Dolly, Haines, Johnathan L., Mayeux, Richard, Vance, Jeffery M., Pericak-Vance, Margaret A., Edwards, Christopher, and Hamilton-Nelson, Kara L.
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- 2017
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217. Transethnic genome-wide scan identifies novel Alzheimer's disease loci.
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Jun, Gyungah R., Chung, Jaeyoon, Mez, Jesse, Barber, Robert, Beecham, Gary W., Bennett, David A., Buxbaum, Joseph D., Byrd, Goldie S., Carrasquillo, Minerva M., Crane, Paul K., Cruchaga, Carlos, De Jager, Philip, Ertekin-Taner, Nilufer, Evans, Denis, Fallin, M. Danielle, Foroud, Tatiana M., Friedland, Robert P., Goate, Alison M., Graff-Radford, Neill R., and Hendrie, Hugh
- 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. [ABSTRACT FROM AUTHOR]
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- 2017
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218. Correction: Whole exome sequencing study identifies novel rare and common Alzheimer’s-Associated variants involved in immune response and transcriptional regulation
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Bis, Joshua C., Jian, Xueqiu, Kunkle, Brian W., Chen, Yuning, Hamilton-Nelson, Kara L., Bush, William S., Salerno, William J., Lancour, Daniel, Ma, Yiyi, Renton, Alan E., Marcora, Edoardo, Farrell, John J., Zhao, Yi, Qu, Liming, Ahmad, Shahzad, Amin, Najaf, Amouyel, Philippe, Beecham, Gary W., Below, Jennifer E., Campion, Dominique, Cantwell, Laura, Charbonnier, Camille, Chung, Jaeyoon, Crane, Paul K., Cruchaga, Carlos, Cupples, L. Adrienne, Dartigues, Jean-François, Debette, Stéphanie, Deleuze, Jean-François, Fulton, Lucinda, Gabriel, Stacey B., Genin, Emmanuelle, Gibbs, Richard A., Goate, Alison, Grenier-Boley, Benjamin, Gupta, Namrata, Haines, Jonathan L., Havulinna, Aki S., Helisalmi, Seppo, Hiltunen, Mikko, Howrigan, Daniel P., Ikram, M. Arfan, Kaprio, Jaakko, Konrad, Jan, Kuzma, Amanda, Lander, Eric S., Lathrop, Mark, Lehtimäki, Terho, Lin, Honghuang, Mattila, Kari, Mayeux, Richard, Muzny, Donna M., Nasser, Waleed, Neale, Benjamin, Nho, Kwangsik, Nicolas, Gaël, Patel, Devanshi, Pericak-Vance, Margaret A., Perola, Markus, Psaty, Bruce M., Quenez, Olivier, Rajabli, Farid, Redon, Richard, Reitz, Christiane, Remes, Anne M., Salomaa, Veikko, Sarnowski, Chloe, Schmidt, Helena, Schmidt, Michael, Schmidt, Reinhold, Soininen, Hilkka, Thornton, Timothy A., Tosto, Giuseppe, Tzourio, Christophe, van der Lee, Sven J., van Duijn, Cornelia M., Valladares, Otto, Vardarajan, Badri, Wang, Li-San, Wang, Weixin, Wijsman, Ellen, Wilson, Richard K., Witten, Daniela, Worley, Kim C., Zhang, Xiaoling, Bellenguez, Celine, Lambert, Jean-Charles, Kurki, Mitja I., Palotie, Aarno, Daly, Mark, Boerwinkle, Eric, Lunetta, Kathryn L., Destefano, Anita L., Dupuis, Josée, Martin, Eden R., Schellenberg, Gerard D., Seshadri, Sudha, Naj, Adam C., Fornage, Myriam, and Farrer, Lindsay A.
- Abstract
A correction to this paper has been published and can be accessed via a link at the top of the paper.
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- 2020
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219. Vitamin D from different sources is inversely associated with Parkinson disease
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Wang, Liyong, primary, Evatt, Marian L., additional, Maldonado, Lizmarie G., additional, Perry, William R., additional, Ritchie, James C., additional, Beecham, Gary W., additional, Martin, Eden R., additional, Haines, Jonathan L., additional, Pericak-Vance, Margaret A., additional, Vance, Jeffery M., additional, and Scott, William K., additional
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- 2014
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220. Effects of Multiple Genetic Loci on Age at Onset in Late-Onset Alzheimer Disease
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Naj, Adam C., primary, Jun, Gyungah, additional, Reitz, Christiane, additional, Kunkle, Brian W., additional, Perry, William, additional, Park, Yo Son, additional, Beecham, Gary W., additional, Rajbhandary, Ruchita A., additional, Hamilton-Nelson, Kara L., additional, Wang, Li-San, additional, Kauwe, John S. K., additional, Huentelman, Matthew J., additional, Myers, Amanda J., additional, Bird, Thomas D., additional, Boeve, Bradley F., additional, Baldwin, Clinton T., additional, Jarvik, Gail P., additional, Crane, Paul K., additional, Rogaeva, Ekaterina, additional, Barmada, M. Michael, additional, Demirci, F. Yesim, additional, Cruchaga, Carlos, additional, Kramer, Patricia L., additional, Ertekin-Taner, Nilufer, additional, Hardy, John, additional, Graff-Radford, Neill R., additional, Green, Robert C., additional, Larson, Eric B., additional, St. George-Hyslop, Peter H., additional, Buxbaum, Joseph D., additional, Evans, Denis A., additional, Schneider, Julie A., additional, Lunetta, Kathryn L., additional, Kamboh, M. Ilyas, additional, Saykin, Andrew J., additional, Reiman, Eric M., additional, De Jager, Philip L., additional, Bennett, David A., additional, Morris, John C., additional, Montine, Thomas J., additional, Goate, Alison M., additional, Blacker, Deborah, additional, Tsuang, Debby W., additional, Hakonarson, Hakon, additional, Kukull, Walter A., additional, Foroud, Tatiana M., additional, Martin, Eden R., additional, Haines, Jonathan L., additional, Mayeux, Richard P., additional, Farrer, Lindsay A., additional, Schellenberg, Gerard D., additional, Pericak-Vance, Margaret A., additional, Albert, Marilyn S., additional, Albin, Roger L., additional, Apostolova, Liana G., additional, Arnold, Steven E., additional, Barber, Robert, additional, Barnes, Lisa L., additional, Beach, Thomas G., additional, Becker, James T., additional, Beekly, Duane, additional, Bigio, Eileen H., additional, Bowen, James D., additional, Boxer, Adam, additional, Burke, James R., additional, Cairns, Nigel J., additional, Cantwell, Laura B., additional, Cao, Chuanhai, additional, Carlson, Chris S., additional, Carney, Regina M., additional, Carrasquillo, Minerva M., additional, Carroll, Steven L., additional, Chui, Helena C., additional, Clark, David G., additional, Corneveaux, Jason, additional, Cribbs, David H., additional, Crocco, Elizabeth A., additional, DeCarli, Charles, additional, DeKosky, Steven T., additional, Dick, Malcolm, additional, Dickson, Dennis W., additional, Duara, Ranjan, additional, Faber, Kelley M., additional, Fallon, Kenneth B., additional, Farlow, Martin R., additional, Ferris, Steven, additional, Frosch, Matthew P., additional, Galasko, Douglas R., additional, Ganguli, Mary, additional, Gearing, Marla, additional, Geschwind, Daniel H., additional, Ghetti, Bernardino, additional, Gilbert, John R., additional, Glass, Jonathan D., additional, Growdon, John H., additional, Hamilton, Ronald L., additional, Harrell, Lindy E., additional, Head, Elizabeth, additional, Honig, Lawrence S., additional, Hulette, Christine M., additional, Hyman, Bradley T., additional, Jicha, Gregory A., additional, Jin, Lee-Way, additional, Karydas, Anna, additional, Kaye, Jeffrey A., additional, Kim, Ronald, additional, Koo, Edward H., additional, Kowall, Neil W., additional, Kramer, Joel H., additional, LaFerla, Frank M., additional, Lah, James J., additional, Leverenz, James B., additional, Levey, Allan I., additional, Li, Ge, additional, Lieberman, Andrew P., additional, Lin, Chiao-Feng, additional, Lopez, Oscar L., additional, Lyketsos, Constantine G., additional, Mack, Wendy J., additional, Martiniuk, Frank, additional, Mash, Deborah C., additional, Masliah, Eliezer, additional, McCormick, Wayne C., additional, McCurry, Susan M., additional, McDavid, Andrew N., additional, McKee, Ann C., additional, Mesulam, Marsel, additional, Miller, Bruce L., additional, Miller, Carol A., additional, Miller, Joshua W., additional, Murrell, Jill R., additional, Olichney, John M., additional, Pankratz, Vernon S., additional, Parisi, Joseph E., additional, Paulson, Henry L., additional, Peskind, Elaine, additional, Petersen, Ronald C., additional, Pierce, Aimee, additional, Poon, Wayne W., additional, Potter, Huntington, additional, Quinn, Joseph F., additional, Raj, Ashok, additional, Raskind, Murray, additional, Reisberg, Barry, additional, Ringman, John M., additional, Roberson, Erik D., additional, Rosen, Howard J., additional, Rosenberg, Roger N., additional, Sano, Mary, additional, Schneider, Lon S., additional, Seeley, William W., additional, Smith, Amanda G., additional, Sonnen, Joshua A., additional, Spina, Salvatore, additional, Stern, Robert A., additional, Tanzi, Rudolph E., additional, Thornton-Wells, Tricia A., additional, Trojanowski, John Q., additional, Troncoso, Juan C., additional, Valladares, Otto, additional, Van Deerlin, Vivianna M., additional, Van Eldik, Linda J., additional, Vardarajan, Badri N., additional, Vinters, Harry V., additional, Vonsattel, Jean Paul, additional, Weintraub, Sandra, additional, Welsh-Bohmer, Kathleen A., additional, Williamson, Jennifer, additional, Wishnek, Sarah, additional, Woltjer, Randall L., additional, Wright, Clinton B., additional, Younkin, Steven G., additional, Yu, Chang-En, additional, and Yu, Lei, additional
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- 2014
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221. P1-036: CLINICAL CHARACTERISTICS OF LATE ONSET ALZHEIMER DISEASE IN AN EXTENDED FAMILY WITH A MISSENSE VARIANT IN TTC3
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Carney, Regina, primary, Kohli, Martin A., additional, Kunkle, Brian W., additional, Martin, Eden R., additional, Beecham, Gary W., additional, Gilbert, John R., additional, and Pericak-Vance, Margaret A., additional
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- 2014
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222. Haplotype-specific modulation of a SOX10/CREB response element at the Charcot–Marie–Tooth disease type 4C locus SH3TC2
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Brewer, Megan Hwa, primary, Ma, Ki Hwan, additional, Beecham, Gary W., additional, Gopinath, Chetna, additional, Baas, Frank, additional, Choi, Byung-Ok, additional, Reilly, Mary M., additional, Shy, Michael E., additional, Züchner, Stephan, additional, Svaren, John, additional, Antonellis, Anthony, additional, Hodonsky, Chani, additional, Quarles, Richard, additional, Fischbeck, Kurt, additional, Lupski, Jim, additional, Inoue, Ken, additional, Wegner, Michael, additional, and Seeman, Pavel, additional
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- 2014
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223. Absence of C9ORF72 expanded or intermediate repeats in autopsy‐confirmed Parkinson's disease
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Nuytemans, Karen, primary, Inchausti, Vanessa, additional, Beecham, Gary W., additional, Wang, Liyong, additional, Dickson, Dennis W., additional, Trojanowski, John Q., additional, Lee, Virginia M.‐Y., additional, Mash, Deborah C., additional, Frosch, Matthew P., additional, Foroud, Tatiana M., additional, Honig, Lawrence S., additional, Montine, Thomas J., additional, Dawson, Ted M., additional, Martin, Eden R., additional, Scott, William K., additional, and Vance, Jeffery M., additional
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- 2014
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224. Meta-analysis of 74,046 individuals identifies 11 new susceptibility loci for Alzheimer's disease
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Lambert, Jean-Charles, Ibrahim-Verbaas, Carla A., Harold, Denise, Naj, Adam C., Sims, Rebecca, Bellenguez, Celine, Jun, Gyungah, DeStefano, Anita L., Bis, Joshua C., Beecham, Gary W., Grenier-Boley, Benjamin, Russo, Giancarlo, Thornton-Wells, Tricia A., Jones, Nicola, Smith, Albert V., Chouraki, Vincent, Thomas, Charlene, Ikram, M. Arfan, Zelenika, Diana, Vardarajan, Badri N., Kamatani, Yoichiro, Lin, Chiao-Feng, Gerrish, Amy, Schmidt, Helena, Kunkle, Brian, Dunstan, Melanie L., Ruiz, Agustin, Bihoreau, Marie-Therese, Choi, Seung-Hoan, Reitz, Christiane, Pasquier, Florence, Hollingworth, Paul, Ramirez, Alfredo, Hanon, Olivier, Fitzpatrick, Annette L., Buxbaum, Joseph D., Campion, Dominique, Crane, Paul K., Baldwin, Clinton, Becker, Tim, Gudnason, Vilmundur, Cruchaga, Carlos, Craig, David, Amin, Najaf, Berr, Claudine, Lopez, Oscar L., De Jager, Philip L., Deramecourt, Vincent, Johnston, Janet A., Evans, Denis, Lovestone, Simon, Letenneur, Luc, Moron, Francisco J., Rubinsztein, David C., Eiriksdottir, Gudny, Sleegers, Kristel, Goate, Alison M., Fievet, Nathalie, Huentelman, Matthew J., Gill, Michael, Brown, Kristelle, Kamboh, M. Ilyas, Keller, Lina, Barberger-Gateau, Pascale, McGuinness, Bernadette, Larson, Eric B., Green, Robert, Myers, Amanda J., Dufouil, Carole, Todd, Stephen, Wallon, David, Love, Seth, Rogaeva, Ekaterina, Gallacher, John, St George-Hyslop, Peter, Clarimon, Jordi, Lleo, Alberto, Bayer, Anthony, Tsuang, Debby W., Yu, Lei, Tsolaki, Magda, Bossu, Paola, Spalletta, Gianfranco, Proitsi, Petroula, Collinge, John, Sorbi, Sandro, Sanchez-Garcia, Florentino, Fox, Nick C., Hardy, John, Naranjo, Maria Candida Deniz, Bosco, Paolo, Clarke, Robert, Brayne, Carol, Galimberti, Daniela, Mancuso, Michelangelo, Matthews, Fiona, Moebus, Susanne, Mecocci, Patrizia, Del Zompo, Maria, Maier, Wolfgang, Hampel, Harald, Pilotto, Alberto, Bullido, Maria, Panza, Francesco, Caffarra, Paolo, Nacmias, Benedetta, Gilbert, John R., Mayhaus, Manuel, Lannfelt, Lars, Hakonarson, Hakon, Pichler, Sabrina, Carrasquillo, Minerva M., Ingelsson, Martin, Beekly, Duane, Alvarez, Victoria, Zou, Fanggeng, Valladares, Otto, Younkin, Steven G., Coto, Eliecer, Hamilton-Nelson, Kara L., Gu, Wei, Razquin, Cristina, Pastor, Pau, Mateo, Ignacio, Owen, Michael J., Faber, Kelley M., Jonsson, Palmi V., Combarros, Onofre, O'Donovan, Michael C., Cantwell, Laura B., Soininen, Hilkka, Blacker, Deborah, Mead, Simon, Mosley, Thomas H., Jr., Bennett, David A., Harris, Tamara B., Fratiglioni, Laura, Holmes, Clive, de Bruijn, Renee F. A. G., Passmore, Peter, Montine, Thomas J., Bettens, Karolien, Rotter, Jerome I., Brice, Alexis, Morgan, Kevin, Foroud, Tatiana M., Kukull, Walter A., Hannequin, Didier, Powell, John F., Nalls, Michael A., Ritchie, Karen, Lunetta, Kathryn L., Kauwe, John S. K., Boerwinkle, Eric, Riemenschneider, Matthias, Boada, Merce, Hiltunen, Mikko, Martin, Eden R., Schmidt, Reinhold, Rujescu, Dan, Wang, Li-San, Dartigues, Jean-Francois, Mayeux, Richard, Tzourio, Christophe, Hofman, Albert, Noethen, Markus M., Graff, Caroline, Psaty, Bruce M., Jones, Lesley, Haines, Jonathan L., Holmans, Peter A., Lathrop, Mark, Pericak-Vance, Margaret A., Launer, Lenore J., Farrer, Lindsay A., van Duijn, Cornelia M., Van Broeckhoven, Christine, Moskvina, Valentina, Seshadri, Sudha, Williams, Julie, Schellenberg, Gerard D., Amouyel, Philippe, Lambert, Jean-Charles, Ibrahim-Verbaas, Carla A., Harold, Denise, Naj, Adam C., Sims, Rebecca, Bellenguez, Celine, Jun, Gyungah, DeStefano, Anita L., Bis, Joshua C., Beecham, Gary W., Grenier-Boley, Benjamin, Russo, Giancarlo, Thornton-Wells, Tricia A., Jones, Nicola, Smith, Albert V., Chouraki, Vincent, Thomas, Charlene, Ikram, M. Arfan, Zelenika, Diana, Vardarajan, Badri N., Kamatani, Yoichiro, Lin, Chiao-Feng, Gerrish, Amy, Schmidt, Helena, Kunkle, Brian, Dunstan, Melanie L., Ruiz, Agustin, Bihoreau, Marie-Therese, Choi, Seung-Hoan, Reitz, Christiane, Pasquier, Florence, Hollingworth, Paul, Ramirez, Alfredo, Hanon, Olivier, Fitzpatrick, Annette L., Buxbaum, Joseph D., Campion, Dominique, Crane, Paul K., Baldwin, Clinton, Becker, Tim, Gudnason, Vilmundur, Cruchaga, Carlos, Craig, David, Amin, Najaf, Berr, Claudine, Lopez, Oscar L., De Jager, Philip L., Deramecourt, Vincent, Johnston, Janet A., Evans, Denis, Lovestone, Simon, Letenneur, Luc, Moron, Francisco J., Rubinsztein, David C., Eiriksdottir, Gudny, Sleegers, Kristel, Goate, Alison M., Fievet, Nathalie, Huentelman, Matthew J., Gill, Michael, Brown, Kristelle, Kamboh, M. Ilyas, Keller, Lina, Barberger-Gateau, Pascale, McGuinness, Bernadette, Larson, Eric B., Green, Robert, Myers, Amanda J., Dufouil, Carole, Todd, Stephen, Wallon, David, Love, Seth, Rogaeva, Ekaterina, Gallacher, John, St George-Hyslop, Peter, Clarimon, Jordi, Lleo, Alberto, Bayer, Anthony, Tsuang, Debby W., Yu, Lei, Tsolaki, Magda, Bossu, Paola, Spalletta, Gianfranco, Proitsi, Petroula, Collinge, John, Sorbi, Sandro, Sanchez-Garcia, Florentino, Fox, Nick C., Hardy, John, Naranjo, Maria Candida Deniz, Bosco, Paolo, Clarke, Robert, Brayne, Carol, Galimberti, Daniela, Mancuso, Michelangelo, Matthews, Fiona, Moebus, Susanne, Mecocci, Patrizia, Del Zompo, Maria, Maier, Wolfgang, Hampel, Harald, Pilotto, Alberto, Bullido, Maria, Panza, Francesco, Caffarra, Paolo, Nacmias, Benedetta, Gilbert, John R., Mayhaus, Manuel, Lannfelt, Lars, Hakonarson, Hakon, Pichler, Sabrina, Carrasquillo, Minerva M., Ingelsson, Martin, Beekly, Duane, Alvarez, Victoria, Zou, Fanggeng, Valladares, Otto, Younkin, Steven G., Coto, Eliecer, Hamilton-Nelson, Kara L., Gu, Wei, Razquin, Cristina, Pastor, Pau, Mateo, Ignacio, Owen, Michael J., Faber, Kelley M., Jonsson, Palmi V., Combarros, Onofre, O'Donovan, Michael C., Cantwell, Laura B., Soininen, Hilkka, Blacker, Deborah, Mead, Simon, Mosley, Thomas H., Jr., Bennett, David A., Harris, Tamara B., Fratiglioni, Laura, Holmes, Clive, de Bruijn, Renee F. A. G., Passmore, Peter, Montine, Thomas J., Bettens, Karolien, Rotter, Jerome I., Brice, Alexis, Morgan, Kevin, Foroud, Tatiana M., Kukull, Walter A., Hannequin, Didier, Powell, John F., Nalls, Michael A., Ritchie, Karen, Lunetta, Kathryn L., Kauwe, John S. K., Boerwinkle, Eric, Riemenschneider, Matthias, Boada, Merce, Hiltunen, Mikko, Martin, Eden R., Schmidt, Reinhold, Rujescu, Dan, Wang, Li-San, Dartigues, Jean-Francois, Mayeux, Richard, Tzourio, Christophe, Hofman, Albert, Noethen, Markus M., Graff, Caroline, Psaty, Bruce M., Jones, Lesley, Haines, Jonathan L., Holmans, Peter A., Lathrop, Mark, Pericak-Vance, Margaret A., Launer, Lenore J., Farrer, Lindsay A., van Duijn, Cornelia M., Van Broeckhoven, Christine, Moskvina, Valentina, Seshadri, Sudha, Williams, Julie, Schellenberg, Gerard D., and Amouyel, Philippe
- Abstract
Eleven susceptibility loci for late-onset Alzheimer's disease (LOAD) were identified by previous studies; however, a large portion of the genetic risk for this disease remains unexplained. We conducted a large, two-stage meta-analysis of genome-wide association studies (GWAS) in individuals of European ancestry. In stage 1, we used genotyped and imputed data (7,055,881 SNPs) to perform meta-analysis on 4 previously published GWAS data sets consisting of 17,008 Alzheimer's disease cases and 37,154 controls. In stage 2, 11,632 SNPs were genotyped and tested for association in an independent set of 8,572 Alzheimer's disease cases and 11,312 controls. In addition to the APOE locus (encoding apolipoprotein E), 19 loci reached genome-wide significance (P < 5 x 10(-8)) in the combined stage 1 and stage 2 analysis, of which 11 are newly associated with Alzheimer's disease.
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- 2013
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225. C9ORF72 intermediate repeat copies are a significant risk factor for Parkinson disease.
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Nuytemans, Karen, Nuytemans, Karen, Bademci, Güney, Kohli, Martin M, Beecham, Gary W, Wang, Liyong, Young, Juan I, Nahab, Fatta, Martin, Eden R, Gilbert, John R, Benatar, Michael, Haines, Jonathan L, Scott, William K, Züchner, Stephan, Pericak-Vance, Margaret A, Vance, Jeffery M, Nuytemans, Karen, Nuytemans, Karen, Bademci, Güney, Kohli, Martin M, Beecham, Gary W, Wang, Liyong, Young, Juan I, Nahab, Fatta, Martin, Eden R, Gilbert, John R, Benatar, Michael, Haines, Jonathan L, Scott, William K, Züchner, Stephan, Pericak-Vance, Margaret A, and Vance, Jeffery M
- Abstract
We set out to determine whether expansions in the C9ORF72 repeat found in amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) families are associated with Parkinson disease (PD). We determined the repeat size in a total of 889 clinically ascertained patients (including PD and essential tremor plus Parkinsonism (ETP)) and 1144 controls using a repeat-primed PCR assay. We found that large C9ORF72 repeat expansions (>30 repeats) were not contributing to PD risk. However, PD and ETP cases had a significant increase in intermediate (>20 to 30+) repeat copies compared to controls. Overall, 14 cases (13 PD, 1 ETP) and three controls had >20 repeat copies (Fisher's exact test p = 0.002). Further, seven cases and no controls had >23 repeat copies (p = 0.003). Our results suggest that intermediate copy numbers of the C9ORF72 repeat contribute to risk for PD and ETP. This also suggests that PD, ALS and FTD share some pathophysiological mechanisms of disease. Further studies are needed to elucidate the contribution of the C9ORF72 repeat in the overall PD population and to determine whether other common genetic risk factors exist between these neurodegenerative disorders.
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- 2013
226. Meta-analysis of 74,046 individuals identifies 11 new susceptibility loci for Alzheimer's disease
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Luxembourg Centre for Systems Biomedicine (LCSB): Bioinformatics Core (R. Schneider Group) [research center], Lambert, Jean-Charles, Ibrahim-Verbaas, Carla A., Harold, Denise, Naj, Adam C., Sims, Rebecca, Bellenguez, Celine, Jun, Gyungah, DeStefano, Anita L., Bis, Joshua C., Beecham, Gary W., Grenier-Boley, Benjamin, Russo, Giancarlo, Thornton-Wells, Tricia A., Jones, Nicola, Smith, Albert V., Chouraki, Vincent, Thomas, Charlene, Ikram, M. Arfan, Zelenika, Diana, Vardarajan, Badri N., Kamatani, Yoichiro, Lin, Chiao-Feng, Gerrish, Amy, Schmidt, Helena, Kunkle, Brian, Dunstan, Melanie L., Ruiz, Agustin, Bihoreau, Marie-Therese, Choi, Seung-Hoan, Reitz, Christiane, Pasquier, Florence, Hollingworth, Paul, Ramirez, Alfredo, Hanon, Olivier, Fitzpatrick, Annette L., Buxbaum, Joseph D., Campion, Dominique, Crane, Paul K., Baldwin, Clinton, Becker, Tim, Gudnason, Vilmundur, Cruchaga, Carlos, Craig, David, Amin, Najaf, Berr, Claudine, Lopez, Oscar L., De Jager, Philip L., Deramecourt, Vincent, Johnston, Janet A., Evans, Denis, Lovestone, Simon, Letenneur, Luc, Moron, Francisco J., Rubinsztein, David C., Eiriksdottir, Gudny, Sleegers, Kristel, Goate, Alison M., Fievet, Nathalie, Huentelman, Matthew J., Gill, Michael, Brown, Kristelle, Kamboh, M. Ilyas, Keller, Lina, Barberger-Gateau, Pascale, McGuinness, Bernadette, Larson, Eric B., Green, Robert, Myers, Amanda J., Dufouil, Carole, Todd, Stephen, Wallon, David, Love, Seth, Rogaeva, Ekaterina, Gallacher, John, St George-Hyslop, Peter, Clarimon, Jordi, Lleo, Alberto, Bayer, Anthony, Tsuang, Debby W., Yu, Lei, Tsolaki, Magda, Bossu, Paola, Spalletta, Gianfranco, Proitsi, Petroula, Collinge, John, Sorbi, Sandro, Sanchez-Garcia, Florentino, Fox, Nick C., Hardy, John, Naranjo, Maria Candida Deniz, Bosco, Paolo, Clarke, Robert, Brayne, Carol, Galimberti, Daniela, Mancuso, Michelangelo, Matthews, Fiona, (EADI), European Alzheimer S Disease Initiative, in Alzheimer's Disease (GERAD), Genetic And Environmental Risk, (ADGC), Alzheimer S Disease Genetic Consortium, in Genomic Epidemiology (CHARGE), Cohorts For Heart And Aging Research, Moebus, Susanne, Mecocci, Patrizia, Del Zompo, Maria, Maier, Wolfgang, Hampel, Harald, Pilotto, Alberto, Bullido, Maria, Panza, Francesco, Caffarra, Paolo, Nacmias, Benedetta, Gilbert, John R., Mayhaus, Manuel, Lannfelt, Lars, Hakonarson, Hakon, Pichler, Sabrina, Carrasquillo, Minerva M., Ingelsson, Martin, Beekly, Duane, Alvarez, Victoria, Zou, Fanggeng, Valladares, Otto, Younkin, Steven G., Coto, Eliecer, Hamilton-Nelson, Kara L., Gu, Wei, Razquin, Cristina, Pastor, Pau, Mateo, Ignacio, Owen, Michael J., Faber, Kelley M., Jonsson, Palmi V., Combarros, Onofre, O'Donovan, Michael C., Cantwell, Laura B., Soininen, Hilkka, Blacker, Deborah, Mead, Simon, Mosley Jr, Thomas H., Bennett, David A., Harris, Tamara B., Fratiglioni, Laura, Holmes, Clive, de Bruijn, Renee F. A. G., Passmore, Peter, Montine, Thomas J., Bettens, Karolien, Rotter, Jerome I., Brice, Alexis, Morgan, Kevin, Foroud, Tatiana M., Kukull, Walter A., Hannequin, Didier, Powell, John F., Nalls, Michael A., Ritchie, Karen, Lunetta, Kathryn L., Kauwe, John S. K., Boerwinkle, Eric, Riemenschneider, Matthias, Boada, Merce, Hiltunen, Mikko, Martin, Eden R., Schmidt, Reinhold, Rujescu, Dan, Wang, Li-San, Dartigues, Jean-Francois, Mayeux, Richard, Tzourio, Christophe, Hofman, Albert, Nothen, Markus M., Graff, Caroline, Psaty, Bruce M., Jones, Lesley, Haines, Jonathan L., Holmans, Peter A., Lathrop, Mark, Pericak-Vance, Margaret A., Launer, Lenore J., Farrer, Lindsay A., van Duijn, Cornelia M., Van Broeckhoven, Christine, Moskvina, Valentina, Seshadri, Sudha, Williams, Julie, Schellenberg, Gerard D., Amouyel, Philippe, Luxembourg Centre for Systems Biomedicine (LCSB): Bioinformatics Core (R. Schneider Group) [research center], Lambert, Jean-Charles, Ibrahim-Verbaas, Carla A., Harold, Denise, Naj, Adam C., Sims, Rebecca, Bellenguez, Celine, Jun, Gyungah, DeStefano, Anita L., Bis, Joshua C., Beecham, Gary W., Grenier-Boley, Benjamin, Russo, Giancarlo, Thornton-Wells, Tricia A., Jones, Nicola, Smith, Albert V., Chouraki, Vincent, Thomas, Charlene, Ikram, M. Arfan, Zelenika, Diana, Vardarajan, Badri N., Kamatani, Yoichiro, Lin, Chiao-Feng, Gerrish, Amy, Schmidt, Helena, Kunkle, Brian, Dunstan, Melanie L., Ruiz, Agustin, Bihoreau, Marie-Therese, Choi, Seung-Hoan, Reitz, Christiane, Pasquier, Florence, Hollingworth, Paul, Ramirez, Alfredo, Hanon, Olivier, Fitzpatrick, Annette L., Buxbaum, Joseph D., Campion, Dominique, Crane, Paul K., Baldwin, Clinton, Becker, Tim, Gudnason, Vilmundur, Cruchaga, Carlos, Craig, David, Amin, Najaf, Berr, Claudine, Lopez, Oscar L., De Jager, Philip L., Deramecourt, Vincent, Johnston, Janet A., Evans, Denis, Lovestone, Simon, Letenneur, Luc, Moron, Francisco J., Rubinsztein, David C., Eiriksdottir, Gudny, Sleegers, Kristel, Goate, Alison M., Fievet, Nathalie, Huentelman, Matthew J., Gill, Michael, Brown, Kristelle, Kamboh, M. Ilyas, Keller, Lina, Barberger-Gateau, Pascale, McGuinness, Bernadette, Larson, Eric B., Green, Robert, Myers, Amanda J., Dufouil, Carole, Todd, Stephen, Wallon, David, Love, Seth, Rogaeva, Ekaterina, Gallacher, John, St George-Hyslop, Peter, Clarimon, Jordi, Lleo, Alberto, Bayer, Anthony, Tsuang, Debby W., Yu, Lei, Tsolaki, Magda, Bossu, Paola, Spalletta, Gianfranco, Proitsi, Petroula, Collinge, John, Sorbi, Sandro, Sanchez-Garcia, Florentino, Fox, Nick C., Hardy, John, Naranjo, Maria Candida Deniz, Bosco, Paolo, Clarke, Robert, Brayne, Carol, Galimberti, Daniela, Mancuso, Michelangelo, Matthews, Fiona, (EADI), European Alzheimer S Disease Initiative, in Alzheimer's Disease (GERAD), Genetic And Environmental Risk, (ADGC), Alzheimer S Disease Genetic Consortium, in Genomic Epidemiology (CHARGE), Cohorts For Heart And Aging Research, Moebus, Susanne, Mecocci, Patrizia, Del Zompo, Maria, Maier, Wolfgang, Hampel, Harald, Pilotto, Alberto, Bullido, Maria, Panza, Francesco, Caffarra, Paolo, Nacmias, Benedetta, Gilbert, John R., Mayhaus, Manuel, Lannfelt, Lars, Hakonarson, Hakon, Pichler, Sabrina, Carrasquillo, Minerva M., Ingelsson, Martin, Beekly, Duane, Alvarez, Victoria, Zou, Fanggeng, Valladares, Otto, Younkin, Steven G., Coto, Eliecer, Hamilton-Nelson, Kara L., Gu, Wei, Razquin, Cristina, Pastor, Pau, Mateo, Ignacio, Owen, Michael J., Faber, Kelley M., Jonsson, Palmi V., Combarros, Onofre, O'Donovan, Michael C., Cantwell, Laura B., Soininen, Hilkka, Blacker, Deborah, Mead, Simon, Mosley Jr, Thomas H., Bennett, David A., Harris, Tamara B., Fratiglioni, Laura, Holmes, Clive, de Bruijn, Renee F. A. G., Passmore, Peter, Montine, Thomas J., Bettens, Karolien, Rotter, Jerome I., Brice, Alexis, Morgan, Kevin, Foroud, Tatiana M., Kukull, Walter A., Hannequin, Didier, Powell, John F., Nalls, Michael A., Ritchie, Karen, Lunetta, Kathryn L., Kauwe, John S. K., Boerwinkle, Eric, Riemenschneider, Matthias, Boada, Merce, Hiltunen, Mikko, Martin, Eden R., Schmidt, Reinhold, Rujescu, Dan, Wang, Li-San, Dartigues, Jean-Francois, Mayeux, Richard, Tzourio, Christophe, Hofman, Albert, Nothen, Markus M., Graff, Caroline, Psaty, Bruce M., Jones, Lesley, Haines, Jonathan L., Holmans, Peter A., Lathrop, Mark, Pericak-Vance, Margaret A., Launer, Lenore J., Farrer, Lindsay A., van Duijn, Cornelia M., Van Broeckhoven, Christine, Moskvina, Valentina, Seshadri, Sudha, Williams, Julie, Schellenberg, Gerard D., and Amouyel, Philippe
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- 2013
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227. Evidence of novel fine-scale structural variation at autism spectrum disorder candidate loci
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Hedges, Dale J, Hedges, Dale J, Hamilton-Nelson, Kara L, Sacharow, Stephanie J, Nations, Laura, Beecham, Gary W, Kozhekbaeva, Zhanna M, Butler, Brittany L, Cukier, Holly N, Whitehead, Patrice L, Ma, Deqiong, Jaworski, James M, Nathanson, Lubov, Lee, Joycelyn M, Hauser, Stephen L, Oksenberg, Jorge R, Cuccaro, Michael L, Haines, Jonathan L, Gilbert, John R, Pericak-Vance, Margaret A, Hedges, Dale J, Hedges, Dale J, Hamilton-Nelson, Kara L, Sacharow, Stephanie J, Nations, Laura, Beecham, Gary W, Kozhekbaeva, Zhanna M, Butler, Brittany L, Cukier, Holly N, Whitehead, Patrice L, Ma, Deqiong, Jaworski, James M, Nathanson, Lubov, Lee, Joycelyn M, Hauser, Stephen L, Oksenberg, Jorge R, Cuccaro, Michael L, Haines, Jonathan L, Gilbert, John R, and Pericak-Vance, Margaret A
- Abstract
Background Autism spectrum disorders (ASD) represent a group of neurodevelopmental disorders characterized by a core set of social-communicative and behavioral impairments. Gamma-aminobutyric acid (GABA) is the major inhibitory neurotransmitter in the brain, acting primarily via the GABA receptors (GABR). Multiple lines of evidence, including altered GABA and GABA receptor expression in autistic patients, indicate that the GABAergic system may be involved in the etiology of autism. Methods As copy number variations (CNVs), particularly rare and de novo CNVs, have now been implicated in ASD risk, we examined the GABA receptors and genes in related pathways for structural variation that may be associated with autism. We further extended our candidate gene set to include 19 genes and regions that had either been directly implicated in the autism literature or were directly related (via function or ancestry) to these primary candidates. For the high resolution CNV screen we employed custom-designed 244 k comparative genomic hybridization (CGH) arrays. Collectively, our probes spanned a total of 11 Mb of GABA-related and additional candidate regions with a density of approximately one probe every 200 nucleotides, allowing a theoretical resolution for detection of CNVs of approximately 1 kb or greater on average. One hundred and sixty-eight autism cases and 149 control individuals were screened for structural variants. Prioritized CNV events were confirmed using quantitative PCR, and confirmed loci were evaluated on an additional set of 170 cases and 170 control individuals that were not included in the original discovery set. Loci that remained interesting were subsequently screened via quantitative PCR on an additional set of 755 cases and 1,809 unaffected family members. Results Results include rare deletions in autistic individuals at JAKMIP1, NRXN1, Neuroligin4Y, OXTR, and ABAT. Common insertion/deletion polymorphisms were detected at several loci, including
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- 2012
228. Common variants at MS4A4/MS4A6E, CD2AP, CD33 and EPHA1 are associated with late-onset Alzheimer's disease.
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Naj, Adam C, Naj, Adam C, Jun, Gyungah, Beecham, Gary W, Wang, Li-San, Vardarajan, Badri Narayan, Buros, Jacqueline, Gallins, Paul J, Buxbaum, Joseph D, Jarvik, Gail P, Crane, Paul K, Larson, Eric B, Bird, Thomas D, Boeve, Bradley F, Graff-Radford, Neill R, De Jager, Philip L, Evans, Denis, Schneider, Julie A, Carrasquillo, Minerva M, Ertekin-Taner, Nilufer, Younkin, Steven G, Cruchaga, Carlos, Kauwe, John SK, Nowotny, Petra, Kramer, Patricia, Hardy, John, Huentelman, Matthew J, Myers, Amanda J, Barmada, Michael M, Demirci, F Yesim, Baldwin, Clinton T, Green, Robert C, Rogaeva, Ekaterina, St George-Hyslop, Peter, Arnold, Steven E, Barber, Robert, Beach, Thomas, Bigio, Eileen H, Bowen, James D, Boxer, Adam, Burke, James R, Cairns, Nigel J, Carlson, Chris S, Carney, Regina M, Carroll, Steven L, Chui, Helena C, Clark, David G, Corneveaux, Jason, Cotman, Carl W, Cummings, Jeffrey L, DeCarli, Charles, DeKosky, Steven T, Diaz-Arrastia, Ramon, Dick, Malcolm, Dickson, Dennis W, Ellis, William G, Faber, Kelley M, Fallon, Kenneth B, Farlow, Martin R, Ferris, Steven, Frosch, Matthew P, Galasko, Douglas R, Ganguli, Mary, Gearing, Marla, Geschwind, Daniel H, Ghetti, Bernardino, Gilbert, John R, Gilman, Sid, Giordani, Bruno, Glass, Jonathan D, Growdon, John H, Hamilton, Ronald L, Harrell, Lindy E, Head, Elizabeth, Honig, Lawrence S, Hulette, Christine M, Hyman, Bradley T, Jicha, Gregory A, Jin, Lee-Way, Johnson, Nancy, Karlawish, Jason, Karydas, Anna, Kaye, Jeffrey A, Kim, Ronald, Koo, Edward H, Kowall, Neil W, Lah, James J, Levey, Allan I, Lieberman, Andrew P, Lopez, Oscar L, Mack, Wendy J, Marson, Daniel C, Martiniuk, Frank, Mash, Deborah C, Masliah, Eliezer, McCormick, Wayne C, McCurry, Susan M, McDavid, Andrew N, McKee, Ann C, Mesulam, Marsel, Miller, Bruce L, Naj, Adam C, Naj, Adam C, Jun, Gyungah, Beecham, Gary W, Wang, Li-San, Vardarajan, Badri Narayan, Buros, Jacqueline, Gallins, Paul J, Buxbaum, Joseph D, Jarvik, Gail P, Crane, Paul K, Larson, Eric B, Bird, Thomas D, Boeve, Bradley F, Graff-Radford, Neill R, De Jager, Philip L, Evans, Denis, Schneider, Julie A, Carrasquillo, Minerva M, Ertekin-Taner, Nilufer, Younkin, Steven G, Cruchaga, Carlos, Kauwe, John SK, Nowotny, Petra, Kramer, Patricia, Hardy, John, Huentelman, Matthew J, Myers, Amanda J, Barmada, Michael M, Demirci, F Yesim, Baldwin, Clinton T, Green, Robert C, Rogaeva, Ekaterina, St George-Hyslop, Peter, Arnold, Steven E, Barber, Robert, Beach, Thomas, Bigio, Eileen H, Bowen, James D, Boxer, Adam, Burke, James R, Cairns, Nigel J, Carlson, Chris S, Carney, Regina M, Carroll, Steven L, Chui, Helena C, Clark, David G, Corneveaux, Jason, Cotman, Carl W, Cummings, Jeffrey L, DeCarli, Charles, DeKosky, Steven T, Diaz-Arrastia, Ramon, Dick, Malcolm, Dickson, Dennis W, Ellis, William G, Faber, Kelley M, Fallon, Kenneth B, Farlow, Martin R, Ferris, Steven, Frosch, Matthew P, Galasko, Douglas R, Ganguli, Mary, Gearing, Marla, Geschwind, Daniel H, Ghetti, Bernardino, Gilbert, John R, Gilman, Sid, Giordani, Bruno, Glass, Jonathan D, Growdon, John H, Hamilton, Ronald L, Harrell, Lindy E, Head, Elizabeth, Honig, Lawrence S, Hulette, Christine M, Hyman, Bradley T, Jicha, Gregory A, Jin, Lee-Way, Johnson, Nancy, Karlawish, Jason, Karydas, Anna, Kaye, Jeffrey A, Kim, Ronald, Koo, Edward H, Kowall, Neil W, Lah, James J, Levey, Allan I, Lieberman, Andrew P, Lopez, Oscar L, Mack, Wendy J, Marson, Daniel C, Martiniuk, Frank, Mash, Deborah C, Masliah, Eliezer, McCormick, Wayne C, McCurry, Susan M, McDavid, Andrew N, McKee, Ann C, Mesulam, Marsel, and Miller, Bruce L
- Abstract
The Alzheimer Disease Genetics Consortium (ADGC) performed a genome-wide association study of late-onset Alzheimer disease using a three-stage design consisting of a discovery stage (stage 1) and two replication stages (stages 2 and 3). Both joint analysis and meta-analysis approaches were used. We obtained genome-wide significant results at MS4A4A (rs4938933; stages 1 and 2, meta-analysis P (P(M)) = 1.7 × 10(-9), joint analysis P (P(J)) = 1.7 × 10(-9); stages 1, 2 and 3, P(M) = 8.2 × 10(-12)), CD2AP (rs9349407; stages 1, 2 and 3, P(M) = 8.6 × 10(-9)), EPHA1 (rs11767557; stages 1, 2 and 3, P(M) = 6.0 × 10(-10)) and CD33 (rs3865444; stages 1, 2 and 3, P(M) = 1.6 × 10(-9)). We also replicated previous associations at CR1 (rs6701713; P(M) = 4.6 × 10(-10), P(J) = 5.2 × 10(-11)), CLU (rs1532278; P(M) = 8.3 × 10(-8), P(J) = 1.9 × 10(-8)), BIN1 (rs7561528; P(M) = 4.0 × 10(-14), P(J) = 5.2 × 10(-14)) and PICALM (rs561655; P(M) = 7.0 × 10(-11), P(J) = 1.0 × 10(-10)), but not at EXOC3L2, to late-onset Alzheimer's disease susceptibility.
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- 2011
229. ALZHEIMER'S DISEASE SEQUENCING PROJECT: SEARCH FOR ALZHEIMER'S DISEASE RESILIENCE GENES THAT MAY MODIFY DISEASE SUSCEPTIBILITY IN SPECIFIC APOE GENOTYPE BACKGROUNDS
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Marcora, Eduardo, Renton, Alan E., Beecham, Gary W., Boerwinkle, Eric, Cantwell, Laura, Cruchaga, Carlos, Cweibel, Rebecca, Felsenfeld, Adam, Fornage, Myriam, Kapoor, Manav, Kauwe, Keoni, Khaladkar, Mugdha, Kobolt, Dan, Ma, Yiyi, Mayeux, Richard, Miller, Marilyn, Naj, Adam C., Partch, Amanda B., Pericak-Vance, Margaret A., Schellenberg, Gerard D., Seshadri, Sudha, Vardarajan, Badri N., Wang, Li-San, Bis, Joshua C., Farrer, Lindsay A., and Goate, Alison M.
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- 2016
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230. MULTIVARIATE PHENOTYPES ASSOCIATION STUDY OF NEUROPATHOLOGICAL FEATURES OF ALZHEIMER'S DISEASE AND RELATED DEMENTIAS
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Chung, Jaeyoon, Ma, Yiyi, Lunetta, Kathryn L., Mez, Jesse, Beecham, Gary W., Pericak-Vance, Margaret A., Haines, Jonathan L., Mayeux, Richard, Schellenberg, Gerard D., Jun, Gyungah R., and Farrer, Lindsay A.
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- 2016
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231. RARE DELETERIOUS AND LOSS-OF-FUNCTION VARIANTS IN OPRL1 AND GAS2L2 CONTRIBUTE TO THE RISK OF LATE-ONSET ALZHEIMER’S DISEASE: ALZHEIMER’S DISEASE SEQUENCING PROJECT CASE-CONTROL STUDY
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Jian, Xueqiu, Bis, Joshua C., Kunkle, Brian W., Hamilton, Kara L., Beecham, Gary W., Bush, William S., Salerno, William, Lancour, Dan, Ma, Yiyi, Chen, Yuning, DeStefano, Anita L., Dupuis, Josee, Boerwinkle, Eric, Schellenberg, Gerard D., Seshadri, Sudha, Naj, Adam C., Fornage, Myriam, and Farrer, Lindsay A.
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- 2016
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232. WHOLE GENOME SEQUENCING IN FAMILIAL LATE-ONSET ALZHEIMER’S DISEASE IDENTIFIES VARIATIONS IN TTC3 AND FSIP2
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Beecham, Gary W., Vardarajan, Badri N., Blue, Elizabeth, Barral, Sandra, Haines, Jonathan L., Bush, William S., van Duijn, Cornelia M., Martin, Eden R., Schellenberg, Gerard D., Mayeux, Richard, Wijsman, Ellen, and Pericak-Vance, Margaret A.
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- 2016
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233. WHOLE EXOME SEQUENCING OF LATE ONSET MULTIPLEX FAMILIES IDENTIFIES RARE CODING VARIANTS IN KNOWN AND NOVEL ALZHEIMER’S DISEASE GENES
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Cukier, Holly N., Kunkle, Brian W., Rolati, Sophie, Whitehead, Patrice L., Vance, Jeffery M., Cuccaro, Michael L., Carney, Regina M., Gilbert, John R., Martin, Eden R., Beecham, Gary W., Haines, Jonathan L., Pericak-Vance, Margaret A., and Hamilton-Nelson, Kara L.
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- 2016
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234. HIGH-RESOLUTION IMPUTATION IN GENOME-WIDE ASSOCIATION STUDIES OF LATE-ONSET ALZHEIMER'S DISEASE IDENTIFIES NOVEL RARE VARIANT ASSOCIATIONS
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Naj, Adam C., Zhao, Yi, van der Lee, Sven J., Hamilton, Kara L., Kunkle, Brian W., Partch, Amanda B., Valladares, Otto, Beecham, Gary W., Martin, Eden R., Wang, Li-San, Haines, Jonathan L., Mayeux, Richard, Farrer, Lindsay A., Pericak-Vance, Margaret A., and Schellenberg, Gerard D.
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- 2016
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235. IDENTIFICATION OF NOVEL CANDIDATE GENES FOR EARLY-ONSET ALZHEIMER'S DISEASE THROUGH INTEGRATED WHOLE-EXOME SEQUENCING AND EXOME CHIP ARRAY ASSOCIATION ANALYSIS
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Kunkle, Brian W., Vardarajan, Badri N., Naj, Adam C., Cukier, Holly N., Dykxhoorn, Derek M., Rolati, Sophie, Whitehead, Patrice L., Carney, Regina M., Cuccaro, Michael L., Vance, Jeffery M., Genetics Consortium, Alzheimer's Disease, Farrer, Lindsay A., Haines, Jonathan L., Schellenberg, Gerard D., Martin, Eden R., Reitz, Christiane, Beecham, Gary W., Mayeux, Richard, and Pericak-Vance, Margaret A.
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- 2016
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236. ABCA7 FRAMESHIFT DELETION ASSOCIATED WITH ALZHEIMER’S DISEASE IN AFRICAN AMERICANS
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Dykxhoorn, Derek M., Cukier, Holly N., Kunkle, Brian W., Vardarajan, Badri N., Rolati, Sophie, Hamilton-Nelson, Kara L., Kohli, Martin A., Whitehead, Patrice L., Van Booven, Derek J., Lang, Rosalyn, Farrer, Lindsay A., Cuccaro, Michael L., Vance, Jeffery M., Gilbert, John R., Beecham, Gary W., Martin, Eden R., Carney, Regina M., Mayeux, Richard, Schellenberg, Gerard D., Byrd, Goldie S., Haines, Jonathan L., and Pericak-Vance, Margaret A.
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- 2016
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237. The CALHM1 P86L Polymorphism is a Genetic Modifier of Age at Onset in Alzheimer's Disease : a Meta-Analysis Study
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Lambert, Jean-Charles, Sleegers, Kristel, Gonzalez-Perez, Antonio, Ingelsson, Martin, Beecham, Gary W., Hiltunen, Mikko, Combarros, Onofre, Bullido, Maria J., Brouwers, Nathalie, Bettens, Karolien, Berr, Claudine, Pasquier, Florence, Richard, Florence, DeKosky, Steven T., Hannequin, Didier, Haines, Jonathan L., Tognoni, Gloria, Fievet, Nathalie, Dartigues, Jean-Francois, Tzourio, Christophe, Engelborghs, Sebastiaan, Arosio, Beatrice, Coto, Elicer, De Deyn, Peter, Del Zompo, Maria, Mateo, Ignacio, Boada, Merce, Antunez, Carmen, Lopez-Arrieta, Jesus, Epelbaum, Jacques, Schjcide, Brit-Marcn Michaud, Frank-Garcia, Ana, Giedraitis, Vilmantas, Helisalmi, Seppo, Porcellini, Elisa, Pilotto, Alberto, Forti, Paola, Ferri, Raffaele, Delepine, Marc, Zelenika, Diana, Lathrop, Mark, Scarpini, Elio, Siciliano, Gabriele, Solfrizzi, Vincenzo, Sorbi, Sandro, Spalletta, Gianfranco, Ravaglia, Giovanni, Valdivieso, Fernando, Vepsäläinen, Saila, Alvarez, Victoria, Bosco, Paolo, Mancuso, Michelangelo, Panza, Francesco, Nacmias, Benedetta, Bossu, Paola, Hanon, Olivier, Piccardi, Paola, Annoni, Giorgio, Mann, David, Marambaud, Philippe, Seripa, Davide, Galimberti, Daniela, Tanzi, Rudolph E., Bertram, Lars, Lendon, Corinne, Lannfelt, Lars, Licastro, Federico, Campion, Dominique, Pericak-Vance, Margaret A., Soininen, Hilkka, Van Broeckhoven, Christine, Alperovitch, Annick, Ruiz, Agustin, Kamboh, M. Ilyas, Amouyel, Philippe, Lambert, Jean-Charles, Sleegers, Kristel, Gonzalez-Perez, Antonio, Ingelsson, Martin, Beecham, Gary W., Hiltunen, Mikko, Combarros, Onofre, Bullido, Maria J., Brouwers, Nathalie, Bettens, Karolien, Berr, Claudine, Pasquier, Florence, Richard, Florence, DeKosky, Steven T., Hannequin, Didier, Haines, Jonathan L., Tognoni, Gloria, Fievet, Nathalie, Dartigues, Jean-Francois, Tzourio, Christophe, Engelborghs, Sebastiaan, Arosio, Beatrice, Coto, Elicer, De Deyn, Peter, Del Zompo, Maria, Mateo, Ignacio, Boada, Merce, Antunez, Carmen, Lopez-Arrieta, Jesus, Epelbaum, Jacques, Schjcide, Brit-Marcn Michaud, Frank-Garcia, Ana, Giedraitis, Vilmantas, Helisalmi, Seppo, Porcellini, Elisa, Pilotto, Alberto, Forti, Paola, Ferri, Raffaele, Delepine, Marc, Zelenika, Diana, Lathrop, Mark, Scarpini, Elio, Siciliano, Gabriele, Solfrizzi, Vincenzo, Sorbi, Sandro, Spalletta, Gianfranco, Ravaglia, Giovanni, Valdivieso, Fernando, Vepsäläinen, Saila, Alvarez, Victoria, Bosco, Paolo, Mancuso, Michelangelo, Panza, Francesco, Nacmias, Benedetta, Bossu, Paola, Hanon, Olivier, Piccardi, Paola, Annoni, Giorgio, Mann, David, Marambaud, Philippe, Seripa, Davide, Galimberti, Daniela, Tanzi, Rudolph E., Bertram, Lars, Lendon, Corinne, Lannfelt, Lars, Licastro, Federico, Campion, Dominique, Pericak-Vance, Margaret A., Soininen, Hilkka, Van Broeckhoven, Christine, Alperovitch, Annick, Ruiz, Agustin, Kamboh, M. Ilyas, and Amouyel, Philippe
- Abstract
The only established genetic determinant of non-Mendelian forms of Alzheimer's disease (AD) is the epsilon 4 allele of the apolipoprotein E gene (APOE). Recently, it has been reported that the P86L polymorphism of the calcium homeostasis modulator 1 gene (CALHM1) is associated with the risk of developing AD. In order to independently assess this association, we performed a meta-analysis of 7,873 AD cases and 13,274 controls of Caucasian origin (from a total of 24 centers in Belgium, Finland, France, Italy, Spain, Sweden, the UK, and the USA). Our results indicate that the CALHM1 P86L polymorphism is likely not a genetic determinant of AD but may modulate age of onset by interacting with the effect of the epsilon 4 allele of the APOE gene.
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- 2010
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238. C9ORF72 Intermediate Repeat Copies Are a Significant Risk Factor for Parkinson Disease
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Nuytemans, Karen, primary, Bademci, Güney, additional, Kohli, Martin M., additional, Beecham, Gary W., additional, Wang, Liyong, additional, Young, Juan I., additional, Nahab, Fatta, additional, Martin, Eden R., additional, Gilbert, John R., additional, Benatar, Michael, additional, Haines, Jonathan L., additional, Scott, William K., additional, Züchner, Stephan, additional, Pericak‐Vance, Margaret A., additional, and Vance, Jeffery M., additional
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- 2013
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239. Global and local ancestry in African-Americans: Implications for Alzheimer's disease risk.
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Hohman, Timothy J., Cooke-Bailey, Jessica N., Reitz, Christiane, Jun, Gyungah, Naj, Adam, Beecham, Gary W., Liu, Zhi, Carney, Regina M., Vance, Jeffrey M., Cuccaro, Michael L., Rajbhandary, Ruchita, Vardarajan, Badri Narayan, Wang, Li-San, Valladares, Otto, Lin, Chiao-Feng, Larson, Eric B., Graff-Radford, Neill R., Evans, Denis, De Jager, Philip L., and Crane, Paul K.
- Abstract
Introduction African-American (AA) individuals have a higher risk for late-onset Alzheimer's disease (LOAD) than Americans of primarily European ancestry (EA). Recently, the largest genome-wide association study in AAs to date confirmed that six of the Alzheimer's disease (AD)-related genetic variants originally discovered in EA cohorts are also risk variants in AA; however, the risk attributable to many of the loci (e.g., APOE, ABCA7) differed substantially from previous studies in EA. There likely are risk variants of higher frequency in AAs that have not been discovered. Methods We performed a comprehensive analysis of genetically determined local and global ancestry in AAs with regard to LOAD status. Results Compared to controls, LOAD cases showed higher levels of African ancestry, both globally and at several LOAD relevant loci, which explained risk for AD beyond global differences. Discussion Exploratory post hoc analyses highlight regions with greatest differences in ancestry as potential candidate regions for future genetic analyses. [ABSTRACT FROM AUTHOR]
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- 2016
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240. Genome-wide linkage analyses of non-Hispanic white families identify novel loci for familial late-onset Alzheimer's disease.
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Kunkle, Brian W., Jaworski, James, Barral, Sandra, Vardarajan, Badri, Beecham, Gary W., Martin, Eden R., Cantwell, Laura S., Partch, Amanda, Bird, Thomas D., Raskind, Wendy H., DeStefano, Anita L., Carney, Regina M., Cuccaro, Michael, Vance, Jeffrey M., Farrer, Lindsay A., Goate, Alison M., Foroud, Tatiana, Mayeux, Richard P., Schellenberg, Gerard D., and Haines, Jonathan L.
- Abstract
Introduction Few high penetrance variants that explain risk in late-onset Alzheimer's disease (LOAD) families have been found. Methods We performed genome-wide linkage and identity-by-descent (IBD) analyses on 41 non-Hispanic white families exhibiting likely dominant inheritance of LOAD, and having no mutations at known familial Alzheimer's disease (AD) loci, and a low burden of APOE ε4 alleles. Results Two-point parametric linkage analysis identified 14 significantly linked regions, including three novel linkage regions for LOAD (5q32, 11q12.2–11q14.1, and 14q13.3), one of which replicates a genome-wide association LOAD locus, the MS4A6A-MS4A4E gene cluster at 11q12.2. Five of the 14 regions (3q25.31, 4q34.1, 8q22.3, 11q12.2–14.1, and 19q13.41) are supported by strong multipoint results (logarithm of odds [LOD*] ≥1.5). Nonparametric multipoint analyses produced an additional significant locus at 14q32.2 (LOD* = 4.18). The 1-LOD confidence interval for this region contains one gene, C14orf177 , and the microRNA Mir_320 , whereas IBD analyses implicates an additional gene BCL11B , a regulator of brain-derived neurotrophic signaling, a pathway associated with pathogenesis of several neurodegenerative diseases. Discussion Examination of these regions after whole-genome sequencing may identify highly penetrant variants for familial LOAD. [ABSTRACT FROM AUTHOR]
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- 2016
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241. Notch activation induces endothelial cell senescence and pro-inflammatory response: Implication of Notch signaling in atherosclerosis
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Liu, Zhao-Jun, primary, Tan, Yurong, additional, Beecham, Gary W., additional, Seo, David M., additional, Tian, Runxia, additional, Li, Yan, additional, Vazquez-Padron, Roberto I., additional, Pericak-Vance, Margaret, additional, Vance, Jeffery M., additional, Goldschmidt-Clermont, Pascal J., additional, Livingstone, Alan S., additional, and Velazquez, Omaida C., additional
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- 2012
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242. Abstract 535: Stem Cell--Mediated Atherosclerosis Plaque Repair
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Liu, Zhao-Jun, primary, Tan, Yurong, additional, Tian, Runxia, additional, Li, Yan, additional, Beecham, Gary W, additional, Seo, David M, additional, Vazquez-Padron, Roberto I, additional, Pericak-Vance, Margaret, additional, Vance, Jeffery M, additional, Goldschmidt-Clermont, Pascal J, additional, Livingstone, Alan S, additional, and Velazquez, Omaida C, additional
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- 2012
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243. Evidence of novel fine-scale structural variation at autism spectrum disorder candidate loci
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Hedges, Dale J, primary, Hamilton-Nelson, Kara L, additional, Sacharow, Stephanie J, additional, Nations, Laura, additional, Beecham, Gary W, additional, Kozhekbaeva, Zhanna M, additional, Butler, Brittany L, additional, Cukier, Holly N, additional, Whitehead, Patrice L, additional, Ma, Deqiong, additional, Jaworski, James M, additional, Nathanson, Lubov, additional, Lee, Joycelyn M, additional, Hauser, Stephen L, additional, Oksenberg, Jorge R, additional, Cuccaro, Michael L, additional, Haines, Jonathan L, additional, Gilbert, John R, additional, and Pericak-Vance, Margaret A, additional
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- 2012
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244. Early-Onset Alzheimer Disease and Candidate Risk Genes Involved in Endolysosomal Transport
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Kunkle, Brian W., Vardarajan, Badri N., Naj, Adam C., Whitehead, Patrice L., Rolati, Sophie, Slifer, Susan, Carney, Regina M., Cuccaro, Michael L., Vance, Jeffery M., Gilbert, John R., Wang, Li-San, Farrer, Lindsay A., Reitz, Christiane, Haines, Jonathan L., Beecham, Gary W., Martin, Eden R., Schellenberg, Gerard D., Mayeux, Richard P., and Pericak-Vance, Margaret A.
- Abstract
IMPORTANCE: Mutations in APP, PSEN1, and PSEN2 lead to early-onset Alzheimer disease (EOAD) but account for only approximately 11% of EOAD overall, leaving most of the genetic risk for the most severe form of Alzheimer disease unexplained. This extreme phenotype likely harbors highly penetrant risk variants, making it primed for discovery of novel risk genes and pathways for AD. OBJECTIVE: To search for rare variants contributing to the risk for EOAD. DESIGN, SETTING, AND PARTICIPANTS: In this case-control study, whole-exome sequencing (WES) was performed in 51 non-Hispanic white (NHW) patients with EOAD (age at onset <65 years) and 19 Caribbean Hispanic families previously screened as negative for established APP, PSEN1, and PSEN2 causal variants. Participants were recruited from John P. Hussman Institute for Human Genomics, Case Western Reserve University, and Columbia University. Rare, deleterious, nonsynonymous, or loss-of-function variants were filtered to identify variants in known and suspected AD genes, variants in multiple unrelated NHW patients, variants present in 19 Hispanic EOAD WES families, and genes with variants in multiple unrelated NHW patients. These variants/genes were tested for association in an independent cohort of 1524 patients with EOAD, 7046 patients with late-onset AD (LOAD), and 7001 cognitively intact controls (age at examination, >65 years) from the Alzheimer’s Disease Genetics Consortium. The study was conducted from January 21, 2013, to October 13, 2016. MAIN OUTCOMES AND MEASURES: Alzheimer disease diagnosed according to standard National Institute of Neurological and Communicative Disorders and Stroke and the Alzheimer Disease and Related Disorders Association criteria. Association between Alzheimer disease and genetic variants and genes was measured using logistic regression and sequence kernel association test–optimal gene tests, respectively. RESULTS: Of the 1524 NHW patients with EOAD, 765 (50.2%) were women and mean (SD) age was 60.0 (4.9) years; of the 7046 NHW patients with LOAD, 4171 (59.2%) were women and mean (SD) age was 77.4 (8.6) years; and of the 7001 NHW controls, 4215 (60.2%) were women and mean (SD) age was 77.4 (8.6) years. The gene PSD2, for which multiple unrelated NHW cases had rare missense variants, was significantly associated with EOAD (P = 2.05 × 10−6; Bonferroni-corrected P value [BP] = 1.3 × 10−3) and LOAD (P = 6.22 × 10−6; BP = 4.1 × 10−3). A missense variant in TCIRG1, present in a NHW patient and segregating in 3 cases of a Hispanic family, was more frequent in EOAD cases (odds ratio [OR], 2.13; 95% CI, 0.99-4.55; P = .06; BP = 0.413), and significantly associated with LOAD (OR, 2.23; 95% CI, 1.37-3.62; P = 7.2 × 10−4; BP = 5.0 × 10−3). A missense variant in the LOAD risk gene RIN3 showed suggestive evidence of association with EOAD after Bonferroni correction (OR, 4.56; 95% CI, 1.26-16.48; P = .02, BP = 0.091). In addition, a missense variant in RUFY1 identified in 2 NHW EOAD cases showed suggestive evidence of an association with EOAD as well (OR, 18.63; 95% CI, 1.62-213.45; P = .003; BP = 0.129). CONCLUSIONS AND RELEVANCE: The genes PSD2, TCIRG1, RIN3, and RUFY1 all may be involved in endolysosomal transport—a process known to be important to development of AD. Furthermore, this study identified shared risk genes between EOAD and LOAD similar to previously reported genes, such as SORL1, PSEN2, and TREM2.
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- 2017
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245. Rare coding variants in PLCG2, ABI3, and TREM2 implicate microglial-mediated innate immunity in Alzheimer's disease
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Sims, Rebecca, van der Lee, Sven J, Naj, Adam C, Bellenguez, Céline, Badarinarayan, Nandini, Jakobsdottir, Johanna, Kunkle, Brian W, Boland, Anne, Raybould, Rachel, Bis, Joshua C, Martin, Eden R, Grenier-Boley, Benjamin, Heilmann-Heimbach, Stefanie, Chouraki, Vincent, Kuzma, Amanda B, Sleegers, Kristel, Vronskaya, Maria, Ruiz, Agustin, Graham, Robert R, Olaso, Robert, Hoffmann, Per, Grove, Megan L, Vardarajan, Badri N, Hiltunen, Mikko, Nöthen, Markus M, White, Charles C, Hamilton-Nelson, Kara L, Epelbaum, Jacques, Maier, Wolfgang, Choi, Seung-Hoan, Beecham, Gary W, Dulary, Cécile, Herms, Stefan, Smith, Albert V, Funk, Cory C, Derbois, Céline, Forstner, Andreas J, Ahmad, Shahzad, Li, Hongdong, Bacq, Delphine, Harold, Denise, Satizabal, Claudia L, Valladares, Otto, Squassina, Alessio, Thomas, Rhodri, Brody, Jennifer A, Qu, Liming, Sánchez-Juan, Pascual, Morgan, Taniesha, Wolters, Frank J, Zhao, Yi, Garcia, Florentino Sanchez, Denning, Nicola, Fornage, Myriam, Malamon, John, Naranjo, Maria Candida Deniz, Majounie, Elisa, Mosley, Thomas H, Dombroski, Beth, Wallon, David, Lupton, Michelle K, Dupuis, Josée, Whitehead, Patrice, Fratiglioni, Laura, Medway, Christopher, Jian, Xueqiu, Mukherjee, Shubhabrata, Keller, Lina, Brown, Kristelle, Lin, Honghuang, Cantwell, Laura B, Panza, Francesco, McGuinness, Bernadette, Moreno-Grau, Sonia, Burgess, Jeremy D, Solfrizzi, Vincenzo, Proitsi, Petra, Adams, Hieab H, Allen, Mariet, Seripa, Davide, Pastor, Pau, Cupples, L Adrienne, Price, Nathan D, Hannequin, Didier, Frank-García, Ana, Levy, Daniel, Chakrabarty, Paramita, Caffarra, Paolo, Giegling, Ina, Beiser, Alexa S, Giedraitis, Vilmantas, Hampel, Harald, Garcia, Melissa E, Wang, Xue, Lannfelt, Lars, Mecocci, Patrizia, Eiriksdottir, Gudny, Crane, Paul K, Pasquier, Florence, Boccardi, Virginia, Henández, Isabel, Barber, Robert C, Scherer, Martin, Tarraga, Lluis, Adams, Perrie M, Leber, Markus, Chen, Yuning, Albert, Marilyn S, Riedel-Heller, Steffi, Emilsson, Valur, Beekly, Duane, Braae, Anne, Schmidt, Reinhold, Blacker, Deborah, Masullo, Carlo, Schmidt, Helena, Doody, Rachelle S, Spalletta, Gianfranco, Jr, W T Longstreth, Fairchild, Thomas J, Bossù, Paola, Lopez, Oscar L, Frosch, Matthew P, Sacchinelli, Eleonora, Ghetti, Bernardino, Yang, Qiong, Huebinger, Ryan M, Jessen, Frank, Li, Shuo, Kamboh, M Ilyas, Morris, John, Sotolongo-Grau, Oscar, Katz, Mindy J, Corcoran, Chris, Dunstan, Melanie, Braddel, Amy, Thomas, Charlene, Meggy, Alun, Marshall, Rachel, Gerrish, Amy, Chapman, Jade, Aguilar, Miquel, Taylor, Sarah, Hill, Matt, Fairén, Mònica Díez, Hodges, Angela, Vellas, Bruno, Soininen, Hilkka, Kloszewska, Iwona, Daniilidou, Makrina, Uphill, James, Patel, Yogen, Hughes, Joseph T, Lord, Jenny, Turton, James, Hartmann, Annette M, Cecchetti, Roberta, Fenoglio, Chiara, Serpente, Maria, Arcaro, Marina, Caltagirone, Carlo, Orfei, Maria Donata, Ciaramella, Antonio, Pichler, Sabrina, Mayhaus, Manuel, Gu, Wei, Lleó, Alberto, Fortea, Juan, Blesa, Rafael, Barber, Imelda S, Brookes, Keeley, Cupidi, Chiara, Maletta, Raffaele Giovanni, Carrell, David, Sorbi, Sandro, Moebus, Susanne, Urbano, Maria, Pilotto, Alberto, Kornhuber, Johannes, Bosco, Paolo, Todd, Stephen, Craig, David, Johnston, Janet, Gill, Michael, Lawlor, Brian, Lynch, Aoibhinn, Fox, Nick C, Hardy, John, Albin, Roger L, Apostolova, Liana G, Arnold, Steven E, Asthana, Sanjay, Atwood, Craig S, Baldwin, Clinton T, Barnes, Lisa L, Barral, Sandra, Beach, Thomas G, Becker, James T, Bigio, Eileen H, Bird, Thomas D, Boeve, Bradley F, Bowen, James D, Boxer, Adam, Burke, James R, Burns, Jeffrey M, Buxbaum, Joseph D, Cairns, Nigel J, Cao, Chuanhai, Carlson, Chris S, Carlsson, Cynthia M, Carney, Regina M, Carrasquillo, Minerva M, Carroll, Steven L, Diaz, Carolina Ceballos, Chui, Helena C, Clark, David G, Cribbs, David H, Crocco, Elizabeth A, DeCarli, Charles, Dick, Malcolm, Duara, Ranjan, Evans, Denis A, Faber, Kelley M, Fallon, Kenneth B, Fardo, David W, Farlow, Martin R, Ferris, Steven, Foroud, Tatiana M, Galasko, Douglas R, Gearing, Marla, Geschwind, Daniel H, Gilbert, John R, Graff-Radford, Neill R, Green, Robert C, Growdon, John H, Hamilton, Ronald L, Harrell, Lindy E, Honig, Lawrence S, Huentelman, Matthew J, Hulette, Christine M, Hyman, Bradley T, Jarvik, Gail P, Abner, Erin, Jin, Lee-Way, Jun, Gyungah, Karydas, Anna, Kaye, Jeffrey A, Kim, Ronald, Kowall, Neil W, Kramer, Joel H, LaFerla, Frank M, Lah, James J, Leverenz, James B, Levey, Allan I, Li, Ge, Lieberman, Andrew P, Lunetta, Kathryn L, Lyketsos, Constantine G, Marson, Daniel C, Martiniuk, Frank, Mash, Deborah C, Masliah, Eliezer, McCormick, Wayne C, McCurry, Susan M, McDavid, Andrew N, McKee, Ann C, Mesulam, Marsel, Miller, Bruce L, Miller, Carol A, Miller, Joshua W, Morris, John C, Murrell, Jill R, Myers, Amanda J, O'Bryant, Sid, Olichney, John M, Pankratz, Vernon S, Parisi, Joseph E, Paulson, Henry L, Perry, William, Peskind, Elaine, Pierce, Aimee, Poon, Wayne W, Potter, Huntington, Quinn, Joseph F, Raj, Ashok, Raskind, Murray, Reisberg, Barry, Reitz, Christiane, Ringman, John M, Roberson, Erik D, Rogaeva, Ekaterina, Rosen, Howard J, Rosenberg, Roger N, Sager, Mark A, Saykin, Andrew J, Schneider, Julie A, Schneider, Lon S, Seeley, William W, Smith, Amanda G, Sonnen, Joshua A, Spina, Salvatore, Stern, Robert A, Swerdlow, Russell H, Tanzi, Rudolph E, Thornton-Wells, Tricia A, Trojanowski, John Q, Troncoso, Juan C, Van Deerlin, Vivianna M, Van Eldik, Linda J, Vinters, Harry V, Vonsattel, Jean Paul, Weintraub, Sandra, Welsh-Bohmer, Kathleen A, Wilhelmsen, Kirk C, Williamson, Jennifer, Wingo, Thomas S, Woltjer, Randall L, Wright, Clinton B, Yu, Chang-En, Yu, Lei, Garzia, Fabienne, Golamaully, Feroze, Septier, Gislain, Engelborghs, Sebastien, Vandenberghe, Rik, De Deyn, Peter P, Fernadez, Carmen Muñoz, Benito, Yoland Aladro, Thonberg, Hakan, Forsell, Charlotte, Lilius, Lena, Kinhult-Stählbom, Anne, Kilander, Lena, Brundin, RoseMarie, Concari, Letizia, Helisalmi, Seppo, Koivisto, Anne Maria, Haapasalo, Annakaisa, Dermecourt, Vincent, Fievet, Nathalie, Hanon, Olivier, Dufouil, Carole, Brice, Alexis, Ritchie, Karen, Dubois, Bruno, Himali, Jayanadra J, Keene, C Dirk, Tschanz, JoAnn, Fitzpatrick, Annette L, Kukull, Walter A, Norton, Maria, Aspelund, Thor, Larson, Eric B, Munger, Ron, Rotter, Jerome I, Lipton, Richard B, Bullido, María J, Hofman, Albert, Montine, Thomas J, Coto, Eliecer, Boerwinkle, Eric, Petersen, Ronald C, Alvarez, Victoria, Rivadeneira, Fernando, Reiman, Eric M, Gallo, Maura, O'Donnell, Christopher J, Reisch, Joan S, Bruni, Amalia Cecilia, Royall, Donald R, Dichgans, Martin, Sano, Mary, Galimberti, Daniela, St George-Hyslop, Peter, Scarpini, Elio, Tsuang, Debby W, Mancuso, Michelangelo, Bonuccelli, Ubaldo, Winslow, Ashley R, Daniele, Antonio, Wu, Chuang-Kuo, Peters, Oliver, Nacmias, Benedetta, Riemenschneider, Matthias, Heun, Reinhard, Brayne, Carol, Rubinsztein, David C, Bras, Jose, Guerreiro, Rita, Al-Chalabi, Ammar, Shaw, Christopher E, Collinge, John, Mann, David, Tsolaki, Magda, Clarimón, Jordi, Sussams, Rebecca, Lovestone, Simon, O'Donovan, Michael C, Owen, Michael J, Behrens, Timothy W, Mead, Simon, Goate, Alison M, Uitterlinden, Andre G, Holmes, Clive, Cruchaga, Carlos, Ingelsson, Martin, Bennett, David A, Powell, John, Golde, Todd E, Graff, Caroline, De Jager, Philip L, Morgan, Kevin, Ertekin-Taner, Nilufer, Combarros, Onofre, Psaty, Bruce M, Passmore, Peter, Younkin, Steven G, Berr, Claudine, Gudnason, Vilmundur, Rujescu, Dan, Dickson, Dennis W, Dartigues, Jean-François, DeStefano, Anita L, Ortega-Cubero, Sara, Hakonarson, Hakon, Campion, Dominique, Boada, Merce, Kauwe, John Keoni, Farrer, Lindsay A, Van Broeckhoven, Christine, Ikram, M Arfan, Jones, Lesley, Haines, Jonathan L, Tzourio, Christophe, Launer, Lenore J, Escott-Price, Valentina, Mayeux, Richard, Deleuze, Jean-François, Amin, Najaf, Holmans, Peter A, Pericak-Vance, Margaret A, Amouyel, Philippe, van Duijn, Cornelia M, Ramirez, Alfredo, Wang, Li-San, Lambert, Jean-Charles, Seshadri, Sudha, Williams, Julie, and Schellenberg, Gerard D
- Abstract
We identified rare coding variants associated with Alzheimer's disease in a three-stage case–control study of 85,133 subjects. In stage 1, we genotyped 34,174 samples using a whole-exome microarray. In stage 2, we tested associated variants (P < 1 × 10−4) in 35,962 independent samples using de novo genotyping and imputed genotypes. In stage 3, we used an additional 14,997 samples to test the most significant stage 2 associations (P < 5 × 10−8) using imputed genotypes. We observed three new genome-wide significant nonsynonymous variants associated with Alzheimer's disease: a protective variant in PLCG2 (rs72824905: p.Pro522Arg, P = 5.38 × 10−10, odds ratio (OR) = 0.68, minor allele frequency (MAF)cases= 0.0059, MAFcontrols= 0.0093), a risk variant in ABI3 (rs616338: p.Ser209Phe, P = 4.56 × 10−10, OR = 1.43, MAFcases= 0.011, MAFcontrols= 0.008), and a new genome-wide significant variant in TREM2 (rs143332484: p.Arg62His, P = 1.55 × 10−14, OR = 1.67, MAFcases= 0.0143, MAFcontrols= 0.0089), a known susceptibility gene for Alzheimer's disease. These protein-altering changes are in genes highly expressed in microglia and highlight an immune-related protein–protein interaction network enriched for previously identified risk genes in Alzheimer's disease. These genetic findings provide additional evidence that the microglia-mediated innate immune response contributes directly to the development of Alzheimer's disease.
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- 2017
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246. PS200. Notch Activation Induces Endothelial Cell Senescence and Pro-Inflammatory Response: Implication of Notch Signaling in Atherosclerosis
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Liu, Zhao-Jun, primary, Tan, Yurong, additional, Tian, Runxia, additional, Li, Yan, additional, Beecham, Gary W., additional, Seo, David M., additional, Vazquez-Padron, Roberto I., additional, Pericak-Vance, Margaret, additional, Vance, Jeffery, additional, Goldschmidt-Clermont, Pascal, additional, Livingstone, Alan S., additional, and Velazquez, Omaida, additional
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- 2011
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247. Comparison of Three Targeted Enrichment Strategies on the SOLiD Sequencing Platform
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Hedges, Dale J., primary, Guettouche, Toumy, additional, Yang, Shan, additional, Bademci, Guney, additional, Diaz, Ashley, additional, Andersen, Ashley, additional, Hulme, William F., additional, Linker, Sara, additional, Mehta, Arpit, additional, Edwards, Yvonne J. K., additional, Beecham, Gary W., additional, Martin, Eden R., additional, Pericak-Vance, Margaret A., additional, Zuchner, Stephan, additional, Vance, Jeffery M., additional, and Gilbert, John R., additional
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- 2011
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248. Common variants at MS4A4/MS4A6E, CD2AP, CD33 and EPHA1 are associated with late-onset Alzheimer's disease
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Naj, Adam C, primary, Jun, Gyungah, additional, Beecham, Gary W, additional, Wang, Li-San, additional, Vardarajan, Badri Narayan, additional, Buros, Jacqueline, additional, Gallins, Paul J, additional, Buxbaum, Joseph D, additional, Jarvik, Gail P, additional, Crane, Paul K, additional, Larson, Eric B, additional, Bird, Thomas D, additional, Boeve, Bradley F, additional, Graff-Radford, Neill R, additional, De Jager, Philip L, additional, Evans, Denis, additional, Schneider, Julie A, additional, Carrasquillo, Minerva M, additional, Ertekin-Taner, Nilufer, additional, Younkin, Steven G, additional, Cruchaga, Carlos, additional, Kauwe, John S K, additional, Nowotny, Petra, additional, Kramer, Patricia, additional, Hardy, John, additional, Huentelman, Matthew J, additional, Myers, Amanda J, additional, Barmada, Michael M, additional, Demirci, F Yesim, additional, Baldwin, Clinton T, additional, Green, Robert C, additional, Rogaeva, Ekaterina, additional, George-Hyslop, Peter St, additional, Arnold, Steven E, additional, Barber, Robert, additional, Beach, Thomas, additional, Bigio, Eileen H, additional, Bowen, James D, additional, Boxer, Adam, additional, Burke, James R, additional, Cairns, Nigel J, additional, Carlson, Chris S, additional, Carney, Regina M, additional, Carroll, Steven L, additional, Chui, Helena C, additional, Clark, David G, additional, Corneveaux, Jason, additional, Cotman, Carl W, additional, Cummings, Jeffrey L, additional, DeCarli, Charles, additional, DeKosky, Steven T, additional, Diaz-Arrastia, Ramon, additional, Dick, Malcolm, additional, Dickson, Dennis W, additional, Ellis, William G, additional, Faber, Kelley M, additional, Fallon, Kenneth B, additional, Farlow, Martin R, additional, Ferris, Steven, additional, Frosch, Matthew P, additional, Galasko, Douglas R, additional, Ganguli, Mary, additional, Gearing, Marla, additional, Geschwind, Daniel H, additional, Ghetti, Bernardino, additional, Gilbert, John R, additional, Gilman, Sid, additional, Giordani, Bruno, additional, Glass, Jonathan D, additional, Growdon, John H, additional, Hamilton, Ronald L, additional, Harrell, Lindy E, additional, Head, Elizabeth, additional, Honig, Lawrence S, additional, Hulette, Christine M, additional, Hyman, Bradley T, additional, Jicha, Gregory A, additional, Jin, Lee-Way, additional, Johnson, Nancy, additional, Karlawish, Jason, additional, Karydas, Anna, additional, Kaye, Jeffrey A, additional, Kim, Ronald, additional, Koo, Edward H, additional, Kowall, Neil W, additional, Lah, James J, additional, Levey, Allan I, additional, Lieberman, Andrew P, additional, Lopez, Oscar L, additional, Mack, Wendy J, additional, Marson, Daniel C, additional, Martiniuk, Frank, additional, Mash, Deborah C, additional, Masliah, Eliezer, additional, McCormick, Wayne C, additional, McCurry, Susan M, additional, McDavid, Andrew N, additional, McKee, Ann C, additional, Mesulam, Marsel, additional, Miller, Bruce L, additional, Miller, Carol A, additional, Miller, Joshua W, additional, Parisi, Joseph E, additional, Perl, Daniel P, additional, Peskind, Elaine, additional, Petersen, Ronald C, additional, Poon, Wayne W, additional, Quinn, Joseph F, additional, Rajbhandary, Ruchita A, additional, Raskind, Murray, additional, Reisberg, Barry, additional, Ringman, John M, additional, Roberson, Erik D, additional, Rosenberg, Roger N, additional, Sano, Mary, additional, Schneider, Lon S, additional, Seeley, William, additional, Shelanski, Michael L, additional, Slifer, Michael A, additional, Smith, Charles D, additional, Sonnen, Joshua A, additional, Spina, Salvatore, additional, Stern, Robert A, additional, Tanzi, Rudolph E, additional, Trojanowski, John Q, additional, Troncoso, Juan C, additional, Van Deerlin, Vivianna M, additional, Vinters, Harry V, additional, Vonsattel, Jean Paul, additional, Weintraub, Sandra, additional, Welsh-Bohmer, Kathleen A, additional, Williamson, Jennifer, additional, Woltjer, Randall L, additional, Cantwell, Laura B, additional, Dombroski, Beth A, additional, Beekly, Duane, additional, Lunetta, Kathryn L, additional, Martin, Eden R, additional, Kamboh, M Ilyas, additional, Saykin, Andrew J, additional, Reiman, Eric M, additional, Bennett, David A, additional, Morris, John C, additional, Montine, Thomas J, additional, Goate, Alison M, additional, Blacker, Deborah, additional, Tsuang, Debby W, additional, Hakonarson, Hakon, additional, Kukull, Walter A, additional, Foroud, Tatiana M, additional, Haines, Jonathan L, additional, Mayeux, Richard, additional, Pericak-Vance, Margaret A, additional, Farrer, Lindsay A, additional, and Schellenberg, Gerard D, additional
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- 2011
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249. GENOME-WIDE ASSOCIATION FOR HYPERTENSION: RESULTS FROM THE MIAMI CARDIOVASCULAR REGISTRY
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Patel, Aarti A., primary, Goldschmidt-Clermont, Pascal J., additional, Sikka, Namrata, additional, Hamilton, Kara, additional, Pericak-Vance, Margaret, additional, Beecham, Gary W., additional, and Seo, David, additional
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- 2011
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250. Identifying Consensus Disease Pathways in Parkinson's Disease Using an Integrative Systems Biology Approach
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Edwards, Yvonne J. K., primary, Beecham, Gary W., additional, Scott, William K., additional, Khuri, Sawsan, additional, Bademci, Guney, additional, Tekin, Demet, additional, Martin, Eden R., additional, Jiang, Zhijie, additional, Mash, Deborah C., additional, ffrench-Mullen, Jarlath, additional, Pericak-Vance, Margaret A., additional, Tsinoremas, Nicholas, additional, and Vance, Jeffery M., additional
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- 2011
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