Citations 77
Factors Associated With the Onset and Persistence of Post–Lumbar Puncture Headache
Monserrate, Andrés E., Ryman, Davis C. , Ma, Sheng‐mei , Noble, James M. , Ringman, John M. , Morris, John C. , Danek, Adrian , Müller‐Sarnowski, Felix, Clifford, David B. , Brooks, William S. , Darby, David , Masters, Colin L. , Weston, Philip S.J. , Farlow, Martin R. , Graff‐Radford, Neill R. , Salloway, Stephen , Fagan, Anne M. , Oliver, Angela , Bateman, Randall J. , Monserrate, Andres E., Xiong, Chengjie , McDade, Eric , Bateman, Randall J , Masters, Colin L , Morris, John C , Brooks, William , Noble, James M
JAMA Neurology | January 26, 2015 | Volume: 72 | Issue: 3 | Pages: 325
Brain amyloidosis ascertainment from cognitive, imaging, and peripheral blood protein measures
Apostolova, Liana G. , Hwang, Kristy , Ávila, David, Elashoff, David , Kohannim, Omid , Teng, Edmond , Sokolow, Sophie , Jack, Clifford R. , Jagust, William, Shaw, Leslie M. , Trojanowski, John Q. , Weiner, Michael W. , Thompson, Paul M. , Initiative, For the Alzheimer's Disease Neuroimaging, Aisen, Paul, Petersen, Ronald , Jagust, Wiliam, Trojanowki, John Q., Gamst, Anthony, Sakin, Andrew J., Potter, William Z., Montine, Tom, Walter, Sarah , Felmlee, Joel P. , Schuff, Norbert, Alexander, Gene E. , DeCarli, Charles, Bandy, Dan, Foster, Norm, Reiman, Eric M. , Mathis, Chet, Cairns, Nigel J., Taylor‐Reinwald, Lisa, Shaw, Lee, Korecka, Magdalena , Crawford, Karen , Neu, Scott, Kornak, John , Kachaturian, Zaven, Frank, Richard , Molchan, Susan, Dolen, Sara, Schneider, Lon S. , Pawluczyk, Sonia, Spann, Bryan M., Brewer, James B., Vanderswag, Helen, Heidebrink, Judith L. , Johnson, Kris , Doody, Rachelle S., Villanueva‐Meyer, Javier , Chowdhury, Munir , Bell, Karen L. , Mintun, Mark A., Schneider, Stacy, Marson, Daniel , Griffith, Randall, Grossman, Hillel, Marzloff, George, deToledo‐Morrell, Leyla, Duara, Ranjan , Varón, Daniel , Robers, Peggy, Albert, Marilyn S. , Kozauer, Nicholas, Zerrate, Maria, Santi, Susan M De, Doraiswamy, P. Murali , Petrella, Jeffrey R. , Aiello, Marilyn, Karlawish, Jason , Smith, Charles D., Given, Curtis A., Hardy, Peter , Oakley, MaryAnn, Simpson, Donna M., Ismail, M. Saleem , Brand, Connie, Richard, Jennifer, Mulnard, Ruth A., Thai, Gaby , Mc-Adams-Ortiz, Catherine, Martin-Cook, Kristen, Devous, Michael D. , Cellar, Janet S., Anderson, Heather S., Laubinger, Mary M., Graff‐Radford, Neill R. , Parfitt, Francine, Farlow, Martin R. , Herring, Scott, Hake, Ann Marie , Dyck, Christopher H. van , MacAvoy, Martha G., Benincasa, Amanda L., Chertkow, Howard, Bergman, Howard , Hosein, Chris, Caldwell, Curtis, Hsiung, Ging‐Yuek Robin , Assaly, Michele, Kertesz, Andrew , Rogers, John, Trost, Dick, Bernick, Charles , Munic, Donna, Wu, Chuang‐Kuo, Johnson, Nancy , Mesulam, Marsel, Sadowsky, Carl, Villena, Teresa, Johnson, Kathleen, Reynolds, Brigid, Rosen, Allyson , Tinklenberg, Jared, Ashford, Wes, Sabbagh, Marwan N. , Connor, Donald J., Jacobson, Sandra A. , Jayam‐Trouth, Annapurni , Lerner, Alan J. , Hudson, Leon, Ogrocki, Paula, Kittur, Smita, Borrie, Michael, Lee, T‐Y, Asthana, Sanjay , Carlsson, Cynthia M., Preda, Adrian , Tariot, Pierre N. , Fleisher, Adam , Reeder, Stephanie, Bates, Vernice, Capote, Horacio, Rainka, Michelle, Hendin, Barry , Kataki, Maria , Zimmerman, Earl A. , Celmins, Dzintra, Brown, Alice D., Blank, Karen, Anderson, Karen, Santulli, Robert B. , Englert, Jessica, Williamson, Jeff D. , Sing, Kaycee M., Watkins, Franklin, Ott, Brian R. , Stopa, Edward G., Tremont, Geoffrey , Salloway, Stephen , Malloy, Paul, Correia, Stephen , Rosen, Howard J. , Mintzer, Jacobo , Longmire, Crystal Flynn, Spicer, Kenneth, Hwang, Kristy S, Shaw, Leslie, Initiative, For the Alzheimer's Disease Neuroimaging, Toga, Arthur W. , Beckett, Laurel , Green, Robert C. , Morris, John C. , Donohue, Michael , Dale, Anders M. , Bernstein, Matt A. , Fox, Nick C. , Koeppe, Robert A. , Chen, Kewei , Mathis, Chet, Lee, Virginia M.‐Y. , Harvey, Danielle , Foroud, Tatiana , Potkin, Steven G. , Shen, Li , Snyder, Peter J. , Kaye, Jeffrey , Quinn, Joseph F. , Lord, Joanne L. , Stern, Yaakov , Honig, Lawrence S. , Clark, David , Tang, Cheuk Ying , Shah, Raj C. , Duara, Ranjan , Rusinek, Henry , Leon, Mony J. de , Arnold, S. R. , Wolk, David A. , López, Oscar L. , Diaz‐Arrastia, Ramon , Levey, Allan I. , Lah, James J. , Burns, Jeffrey M. , Silverman, Daniel H.S. , Johnson, Heather K. , Black, Sandra E. , Stefanovic, Bojana , Feldman, Howard , Martínez, Walter Fabián , Turner, Raymond Scott , Sperling, Reisa Anne , Rentz, Dorene M. , Johnson, Keith A. , Killiany, Ronald , Norbash, Alexander , Nair, Anil K. , Obisesan, Thomas O. , Wang, Paul C. , Fletcher, Evan M. , Carmichael, Owen , Bartha, Robert , Johnson, Sterling C. , Carlsson, Cynthia M. , Nguyen, Dana R. , Reeder, Stephanie, Scharre, Douglas W. , Pearlson, Godfrey D. , Sing, Kaycee M., Miller, Bruce L. , Jack, Clifford R , Preda, Adrian , Thompson, Paul M , Hsiung, Gink-Yuek
Neurology | January 22, 2015 | Volume: 84 | Issue: 7 | Pages: 729-737
Protective variant for hippocampal atrophy identified by whole exome sequencing
Kim, Sungeun , Risacher, Shannon L. , Shen, Li , Corneveaux, Jason J., Swaminathan, Shanker , Lin, Hai , Inlow, Mark , Siniard, Ashley L., Reiman, Rebecca, Aisen, Paul, Petersen, Ronald , Jack, Clifford R. , Weiner, Michael W. , Baldwin, Clinton T., Lunetta, Kathryn L. , Farrer, Lindsay A. , Furney, Simon J. , Lovestone, Simon , Simmons, Andrew , Mecocci, Patrizia , Vellas, Bruno , Tsolaki, Magda , Kłoszewska, Iwona, McDonald, Brenna C. , Farlow, Martin R. , Study, for the Indiana Memory and Aging, Huentelman, Matthew J. , Saykin, Andrew J. , Initiative, for the Alzheimer's Disease Neuroimaging, Nho, Kwangsik T. , Ramanan, Vijay K. , Liu, Yunlong , Foroud, Tatiana , Green, Robert C. , Soininen, Hilkka S. , Ghetti, Bernardino , Study, for the Indiana Memory and Aging, Initiative, for the Alzheimer's Disease Neuroimaging, Jack, Clifford R , Saykin, Andrew J , Shen, Li , Tsolaki, Magda , Mecocci, Patrizia
Annals of Neurology | January 5, 2015 | Volume: 77 | Issue: 3 | Pages: 547-552
We used whole‐exome sequencing to identify variants other than APOE associated with the rate of hippocampal atrophy in amnestic mild cognitive impairment. An in‐silico predicted missense variant in REST (rs3796529) was found exclusively in subjects with slow hippocampal volume loss and validated using unbiased whole‐brain analysis and meta‐analysis across 5 independent cohorts. REST is a master regulator of neurogenesis and neuronal differentiation that has not been previously implicated in Alzheimer's disease. These findings nominate REST and its functional pathways as protective and illustrate the potential of combining next‐generation sequencing with neuroimaging to discover novel disease mechanisms and potential therapeutic targets. Ann Neurol 2015;77:547–552
Rarity of the Alzheimer Disease–ProtectiveAPPA673T Variant in the United States
Wang, Li-San, Graham, Robert , Crane, Paul K. , Kunkle, Brian W. , Cruchaga, Carlos , Murcia, Josue D. Gonzalez , Cannon‐Albright, Lisa , Baldwin, Clinton T., Blennow, Kaj , Kukull, Walter A. , Faber, Kelley M., Schupf, Nicole , Norton, Maria C. , Tschanz, JoAnn T. , Munger, Ronald G. , Corcoran, Christopher, Lin, Chiao‐Feng , Dombroski, Beth A. , Cantwell, Laura B., Partch, Amanda, Håkonarson, Håkon , George‐Hyslop, Peter St , Goate, Alison , Foroud, Tatiana, Carney, Regina M., Larson, Eric B., Behrens, Timothy W. , Kauwe, John, Haines, Jonathan L. , Farrer, Lindsay A. , Pericak‐Vance, Margaret A. , Mayeux, Richard , Schellenberg, Gerard D., Albert, Marilyn S. , Albin, Roger L. , Apostolova, Liana G. , Arnold, Steven E. , Barber, Robert W., Barmada, M. Michael , Beach, Thomas G. , Beecham, Gary W. , Beekly, Duane, Bennett, David A. , Bigio, Eileen H. , Bird, Thomas D., Blacker, Deborah , Bowen, James D. , Boxer, Adam, Buxbaum, Joseph D. , Cairns, Nigel J. , Cao, Chuanhai , Carlson, Chris , Carroll, Steven L. , Chui, Helena C., Clark, David G., Cribbs, David H. , DeCarli, Charles , DeKosky, Steven T. , Demirci, F. Yesim , Dick, Malcolm, Duara, Ranjan , Ertekin‐Taner, Nilüfer , Fallon, Kenneth B., Farlow, Martin R. , Ferris, Steven H. , Frosch, Matthew P. , Gearing, Marla , Geschwind, Daniel H. , Gilbert, John R., Glass, Jonathan D. , Graff‐Radford, Neill R. , Growdon, John H., Hamilton, Ronald L. , Hamilton‐Nelson, Kara L., Harrell, Lindy E., Hulette, Christine M., Jicha, Gregory A. , Jin, Lee‐Way, Jun, Gyungah , Kamboh, M. Ilyas , Karydas, Anna, Koo, Edward H. , Kowall, Neil W. , Kramer, Joel H. , Kramer, Patricia, LaFerla, Frank M. , Leverenz, James B. , Lieberman, Andrew P. , Lunetta, Kathryn L. , Lyketsos, Constantine G. , Mack, Wendy J. , Marson, Daniel , Martin, Eden R. , Martiniuk, Frank , Mash, Deborah C. , Masliah, Eliezer , McCormick, Wayne C., McKee, Ann C. , Miller, Carol A., Miller, Joshua W., Montine, Thomas J. , Morris, John C. , Murrell, Jill R. , Olichney, John , Parisi, Joseph E., Peskind, Elaine R. , Petersen, Ronald , Pierce, Aimee, Poon, Wayne W. , Raj, Ashok , Raskind, Murray A. , Reiman, Eric M. , Reisberg, Barry , Reitz, Christiane , Ringman, John M. , Rosen, Howard J., Rosenberg, Roger N., Sano, Mary , Saykin, Andrew J. , Schneider, Lon S. , Smith, Amanda , Sonnen, Joshua A. , Stern, Robert A. , Tanzi, Rudolph E. , Thornton‐Wells, Tricia A., Trojanowski, John Q. , Troncoso, Juan C. , Tsuang, Debby W. , Vinters, Harry V. , Vonsattel, Jean Paul, Weıntraub, Sandra , Wishnek, Sarah, Woltjer, Randall L. , Wright, Clinton B., Younkin, Steven G., Yu, Chang‐En , Yu, Lei , DeCarli, Charles , Wang, Li-San, Naj, Adam Christian , Cruchaga, Carlos , Zetterberg, Henrik , Rogaeva, Ekaterina A. , Valladares, Otto , Green, Robert C. , Barnes, Lisa L. , Becker, James T. , Boeve, Bradley F. , Burke, James R. , Chui, Helena C. , Crocco, Elizabeth , Dickson, Dennis W. , Duara, Ranjan , Galasko, Douglas , Ganguli, Mary , Ghetti, Bernardino , Hamilton‐Nelson, Kara L. , Head, Elizabeth , Honig, Lawrence S. , Hyman, Bradley T. , Jarvik, Gail P. , Kaye, Jeffrey , Kim, Ronald , Lah, James J. , Levey, Allan I. , Li, Ge , López, Oscar L. , McCurry, Susan M. , McDavid, Andrew , Mesulam, Marsel M. , Miller, Bruce L. , Perry, William , Potter, Huntington , Quinn, Joseph F. , Roberson, Erik D. , Schneider, Julie A. , Seeley, William W. , Spina, Salvatore , Deerlin, Vivianna M. Van , Eldik, Linda J. Van , Vardarajan, Badri Narayan , Welsh-Bohmer, Kathleen Anne , Williamson, Jennifer , Bennett, David A. , Hakonarson, Hakon , Saykin, Andrew J , Leverenz, James B , Cannon-Albright, Lisa A , Stern, Robert A , Morris, John C , Goate, Alison M , Jicha, Gregory A , Sonnen, Joshua
JAMA Neurology | December 22, 2014 | Volume: 72 | Issue: 2 | Pages: 209
Effects of Multiple Genetic Loci on Age at Onset in Late-Onset Alzheimer Disease
Jun, Gyungah , Reitz, Christiane, Kunkle, Brian W. , Park, Yo Son, Beecham, Gary W. , Rajbhandary, Ruchita, Hamilton‐Nelson, Kara L., Wang, Li-San, Kauwe, John, Huentelman, Matthew J. , Bird, Thomas D., Baldwin, Clinton T., Jarvik, Gail P. , Crane, Paul K. , Barmada, M. Michael , Demirci, F. Yesim , Cruchaga, Carlos , Kramer, Patricia L., Ertekin‐Taner, Nilüfer , Hardy, John , Graff‐Radford, Neill R. , Larson, Eric B., George‐Hyslop, Peter St , Buxbaum, Joseph D. , Evans, Denis A., Lunetta, Kathryn L. , Kamboh, M. Ilyas , Saykin, Andrew J. , Reiman, Eric M. , Jager, Philip L. De , Morris, John C. , Montine, Thomas J. , Goate, Alison , Blacker, Deborah , Tsuang, Debby W. , Håkonarson, Håkon , Kukull, Walter A. , Foroud, Tatiana, Martin, Eden R. , Haines, Jonathan L. , Mayeux, Richard , Farrer, Lindsay A. , Schellenberg, Gerard D., Pericak‐Vance, Margaret A. , Albert, Marilyn S. , Albin, Roger L. , Apostolova, Liana G. , Arnold, Steven E. , Barber, Robert W., Beach, Thomas G. , Beekly, Duane, Bigio, Eileen H. , Bowen, James D. , Boxer, Adam, Cairns, Nigel J. , Cantwell, Laura B., Cao, Chuanhai , Carlson, Chris , Carney, Regina M., Carrasquillo, Minerva M., Carroll, Steven L. , Chui, Helena C., Clark, David G., Corneveaux, Jason J., Cribbs, David H. , DeCarli, Charles , DeKosky, Steven T. , Dick, Malcolm, Duara, Ranjan , Faber, Kelley M., Fallon, Kenneth B., Farlow, Martin R. , Ferris, Steven H. , Frosch, Matthew P. , Gearing, Marla , Geschwind, Daniel H. , Gilbert, John R., Glass, Jonathan D. , Growdon, John H., Hamilton, Ronald L. , Harrell, Lindy E., Hulette, Christine M., Jicha, Gregory A. , Jin, Lee‐Way, Karydas, Anna, Koo, Edward H. , Kowall, Neil W. , Kramer, Joel H. , LaFerla, Frank M. , Leverenz, James B. , Li, Ge , Lieberman, Andrew P. , Lin, Chiao‐Feng , Lyketsos, Constantine G. , Mack, Wendy J. , Martiniuk, Frank , Mash, Deborah C. , Masliah, Eliezer , McCormick, Wayne C., McKee, Ann C. , Miller, Carol A., Miller, Joshua W., Murrell, Jill R. , Olichney, John , Parisi, Joseph E., Paulson, Henry L. , Peskind, Elaine R. , Petersen, Ronald , Pierce, Aimee, Poon, Wayne W. , Raj, Ashok , Raskind, Murray A. , Reisberg, Barry , Ringman, John M. , Rosen, Howard J., Rosenberg, Roger N., Sano, Mary , Schneider, Lon S. , Smith, Amanda , Sonnen, Joshua A. , Stern, Robert A. , Tanzi, Rudolph E. , Thornton‐Wells, Tricia A., Trojanowski, John Q. , Troncoso, Juan C. , Vinters, Harry V. , Vonsattel, Jean Paul, Weıntraub, Sandra , Wishnek, Sarah, Woltjer, Randall L. , Wright, Clinton B., Younkin, Steven G., Yu, Chang‐En , Yu, Lei, Bennett, David A. , DeCarli, Charles , Pankratz, Vernon S, Naj, Adam Christian , Perry, William , Hamilton‐Nelson, Kara L. , Wang, Li-San, Myers, Amanda , Boeve, Bradley F. , Rogaeva, Ekaterina A. , Cruchaga, Carlos , Kramer, P. L., Green, Robert C. , Schneider, Julie A. , Bennett, David , Barnes, Lisa L. , Becker, James T. , Burke, James R. , Carrasquillo, Minerva M. , Chui, Helena C. , Crocco, Elizabeth , Dickson, Dennis W. , Duara, Ranjan , Galasko, Douglas , Ganguli, Mary , Ghetti, Bernardino , Head, Elizabeth , Honig, Lawrence S. , Hyman, Bradley T. , Kaye, Jeffrey , Kim, Ronald , Lah, James J. , Levey, Allan I. , López, Oscar L. , McCurry, Susan M. , McDavid, Andrew , Mesulam, Marsel M. , Miller, Bruce L. , Pankratz, V. Shane , Potter, Huntington , Quinn, Joseph F. , Roberson, Erik D. , Seeley, William W. , Spina, Salvatore , Valladares, Otto , Deerlin, Vivianna M. Van , Eldik, Linda J. Van , Vardarajan, Badri Narayan , Welsh-Bohmer, Kathleen Anne , Williamson, Jennifer , Bennett, David A. , Hakonarson, Hakon , Saykin, Andrew J , Leverenz, James B , Jarvik, Gail P , Paulson, Henry L , Stern, Robert A , Hardy, John , Morris, John C , Goate, Alison M , Jicha, Gregory A , Sonnen, Joshua
JAMA Neurology | September 8, 2014 | Volume: 71 | Issue: 11 | Pages: 1394
Age-Specific Incidence Rates for Dementia and Alzheimer Disease in NIA-LOAD/NCRAD and EFIGA Families
Faber, Kelley M., Bird, Thomas D., Bennett, David A. , Rosenberg, Roger N., Graff‐Radford, Neill R. , Goate, Alison , Farlow, Martin R. , Lantigua, Rafael , Medrano, Martin , Ottman, Ruth , Schaid, Daniel J. , Mayeux, Richard , Vardarajan, Badri Narayan , Boeve, Bradley F. , Sweet, Robert A. , Foroud, Tatiana , Bennett, David A. , Goate, Alison M
JAMA Neurology | January 14, 2014 | Volume: 71 | Issue: 3 | Pages: 315
O3–01–03: Protective variant for rate of hippocampal volume loss identified by whole exome sequencing in APOE‐ε3ε3 males with MCI
Corneveaux, Jason J., Lin, Hai , Inlow, Mark , Reiman, Rebecca, Aisen, Paul, Petersen, Ronald, Weiner, Michael W. , Baldwin, Clinton T., Simmons, Andrew , Vellas, Bruno , Kłoszewska, Iwona, Farlow, Martin R. , Huentelman, Matthew J. , Nho, Kwangsik T. , Kim, Sungeun , Risacher, Shannon L. , Shen, Li , Swaminathan, Shanker , Ramanan, Vijay K. , Liu, Yunlong , Foroud, Tatiana , Green, Robert C. , Jack, Clifford R. , Farrer, Lindsay A. , Lovestone, Simon , Mecocci, Patrizia , Tsolaki, Magda , Soininen, Hilkka S. , McDonald, Brenna C. , Saykin, Andrew J.
Alzheimer's & Dementia | October 9, 2013 | Volume: 9 | Issue: 4S_Part_13 | Pages: No page available
P3–194: Age‐specific incidence rates of Alzheimer's disease in family members participating in the NIA‐LOAD genetics study
Bird, Thomas D., Farlow, Martin R. , Graff‐Radford, Neill, Rosenberg, Roger N., Schaid, Daniel J. , Bennett, Jeffrey, Davis, Barb, Faber, Kelley , Garland, Connie, Horner, Kimberly , Kistler, Dana, Kuntz, Karen M. , Levitch, Denise, Norton, Joanne, Pluff, Lindsay, Reyes, Dolly, Rumbaugh, Malia, Sena, Amanda, Torneten, Sarah, Weamer, Elise A., Group, NIA LOAD Study, Mayeux, Richard, Vardarajan, Badri Narayan , Bennett, David A. , Boeve, Bradley F. , Foroud, Tatiana , Goate, Alison , Graff‐Radford, Neill, Ottman, Ruth , Sweet, Robert A. , Tsuang, Debby W. , Group, NIA LOAD Study, Mayeux, Richard
Alzheimer's & Dementia | October 9, 2013 | Volume: 9 | Issue: 4S_Part_15 | Pages: No page available
P3–008: Genome‐wide analysis of genetic variants associated with depressive symptoms in older adults
Mackin, Scott, Aisen, Paul, Petersen, Ronald, Weiner, Michael W. , Farlow, Martin R. , Gao, Sujuan , Nho, Kwangsik T. , Swaminathan, Shanker , Kim, Sungeun , Risacher, Shannon L. , Ramanan, Vijay K. , Shen, Li , McDonald, Brenna C. , Ghetti, Bernardino , Saykin, Andrew J. , Green, Robert C.
Alzheimer's & Dementia | October 9, 2013 | Volume: 9 | Issue: 4S_Part_14 | Pages: No page available
Genome-wide scan of healthy human connectome discovers SPON1 gene variant influencing dementia severity
Jahanshad, Neda , Rajagopalan, Priya , Hua, Xue , Hibar, Derrek P., Nir, Talia M. , Toga, Arthur W. , Jack, Clifford R., Saykin, Andrew J. , Weiner, Michael W. , Medland, Sarah E. , Montgomery, Grant W. , Hansell, Narelle K. , McMahon, Katie L. , Zubicaray, Greig I. de , Martin, Nicholas G. , Wright, Margaret J. , Thompson, Paul M. , Initiative, the Alzheimer’s Disease Neuroimaging, Aisen, Paul, Petersen, Ronald, Jagust, William J. , Trojanowski, John Q. , Toga, Arthur W., Green, Robert C., Liu, Enchi , Green, Robert C., Montine, Tom, Gamst, Anthony, Thomas, Ronald G. , Donohue, Michael, Walter, Sarah , Gessert, Devon, Sather, Tamie, Harvey, Danielle, Donohue, Michael, Kornak, John , Jack, Clifford R., Felmlee, Joel P. , Schuff, Norbert, Alexander, Gene, DeCarli, Charles , Bandy, Dan, Foster, Norm, Reiman, Eric M. , Mathis, Chet, Cairns, Nigel J. , Taylor‐Reinwald, Lisa, Trojanowki, John Q., Shaw, Les, Korecka, Magdalena , Toga, Arthur W., Crawford, Karen , Neu, Scott, Khachaturian, Zaven S., Frank, R.T., Molchan, Susan, Quinn, Joseph, Lind, Betty, Dolen, Sara, Schneider, Lon S. , Pawluczyk, Sonia, Spann, Bryan M., Brewer, James, Vanderswag, Helen, Heidebrink, Judith L. , Johnson, Kris , Doody, Rachelle S., Chowdhury, Munir , Bell, Karen L. , Carroll, Maria , Leon, Sue, Mintun, Mark A., Schneider, Stacy, Marson, Daniel , Griffith, Randall, Clark, David, Grossman, Hillel, Mitsis, Effie, Romirowsky, Aliza, deToledo‐Morrell, Leyla, Duara, Ranjan , Varon, Daniel, Roberts, Peggy, Albert, Marilyn, Onyike, Chiadi, Kielb, Stephanie , Glodzik, Lidia , Santi, Susan De , Doraiswamy, P. Murali , Petrella, Jeffrey R. , Coleman, Robert E. , Arnold, Steven E. , Karlawish, Jason H., Smith, Charles D., Jicha, Gregory A. , Hardy, Peter , Lopez, Oscar L., Oakley, MaryAnn, Simpson, Donna M., Goldstein, Bonnie S., Martin, Kim, Makino, Kelly M., Ismail, M. Saleem , Brand, Connie, Mulnard, Ruth A., Thai, Gaby , Mc-Adams-Ortiz, Catherine, Mathews, Dana, Quiceno, Mary , King, Richard, Martin-Cook, Kristen, Devous, Michael D. , Cellar, Janet S., Anderson, Heather S., Swerdlow, Russell H. , Apostolova, Liana , Lu, Po H. , Bartzokis, George, Graff‐Radford, Neill R. , Parfitt, Francine, Farlow, Martin R. , Hake, Ann Marie , Matthews, Brandy R., Herring, Scott, Dyck, Christopher H. van , Carson, Richard E. , MacAvoy, Martha G., Chertkow, Howard , Bergman, Howard , Hosein, Chris, Caldwell, Curtis, Hsiung, Ging‐Yuek Robin , Feldman, Howard J., Mudge, Benita, Assaly, Michele, Kertesz, Andrew, Rogers, John, Trost, Dick, Bernick, Charles , Munic, Donna, Mesulam, Marek-Marsel, Lipowski, Kristina, Wu, Chuang‐Kuo, Johnson, Nancy E., Sadowsky, Carl, Villena, Teresa, Johnson, Kathleen, Reynolds, Brigid, Marshall, Gad A. , Frey, Meghan , Yesavage, Jerome A. , Taylor, Joy L. , Lane, Barton , Rosen, Allyson , Tinklenberg, Jared, Sabbagh, Marwan, Belden, Christine M. , Jacobson, Sandra A. , Kowall, Neil W. , Budson, Andrew E. , Johnson, Patricia Lynn, Wolday, Saba, Bwayo, Salome K., Lerner, Alan J. , Hudson, Leon, Ogrocki, Paula, Fletcher, Evan, Olichney, John , Kittur, Smita, Borrie, Michael, Lee, T.-Y., Bartha, Robert , Asthana, Sanjay , Carlsson, Cynthia M., Preda, Adrian , Tariot, Pierre N. , Fleisher, Adam , Reeder, Stephanie, Bates, Vernice, Capote, Horacio, Rainka, Michelle, Kataki, Maria , Zimmerman, Earl A. , Celmins, Dzintra, Brown, Alice D., Blank, Karen, Anderson, Karen, Santulli, Robert B. , Schwartz, Eben S., Williamson, Jeff D. , Garg, Pradeep , Watkins, Franklin, Ott, Brian R. , Querfurth, Henry, Tremont, Geoffrey , Salloway, Stephen , Malloy, Paul, Correia, Stephen , Rosen, Howard J., Mintzer, Jacobo , Longmire, Crystal Flynn, Spicer, Kenneth, Rachinsky, Irina, Kertesz, Andrew, Drost, Dick, Lee, Ting‐Yim , Jack, Clifford R., Green, Robert C. , Initiative, the Alzheimer’s Disease Neuroimaging, Jack, Clifford R. , Toga, Arthur W., Beckett, Laurel , Green, Robert C., Morris, John C. , Green, Robert C., Donohue, Michael, Sather, Tamie, Donohue, Michael, Jack, Clifford R., Dale, Anders M. , Bernstein, Matt A. , Fox, Nick C. , Koeppe, Robert A. , Chen, Kewei , Mathis, Chet, Lee, Virginia M.‐Y. , Toga, Arthur W., Foroud, Tatiana , Potkin, Steven G. , Shen, Li , Snyder, Peter J. , Kaye, Jeffrey , Lord, Joanne L. , Villanueva-Meyer, Javier E. , Stern, Yaakov , Honig, Lawrence S. , Ances, Beau M. , Grossman, Hillel, Shah, Raj C. , Duara, Ranjan , Varón, Daniel , Rusinek, Henry , Leon, Mony J. de , Karlawish, Jason , Wolk, David A. , Porsteinsson, Anton P. , Womack, Kyle , Diaz‐Arrastia, Ramon , Weiner, Myron , Levey, Allan I. , Lah, James J. , Burns, Jeffrey M. , Silverman, Daniel H.S. , Johnson, Heather M. , Black, Sandra E. , Stefanovic, Bojana , Kertesz, Andrew, Kerwin, Diana , Martínez, Walter Fabián , Turner, Raymond Scott , Sperling, Reisa Anne , Johnson, Keith A. , Killiany, Ronald , Norbash, Alexander , Obisesan, Thomas O. , Carmichael, Owen , Johnson, Sterling C. , Nguyen, Dana R. , Reeder, Stephanie, Scharre, Douglas W. , Pearlson, Godfrey D. , Sink, Kaycee M. , Miller, Bruce L. , Finger, Elizabeth C. , Kertesz, Andrew, de Zubicaray, Greig I , Hansell, Narelle K , Saykin, Andrew J , Preda, Adrian , Martin, Nicholas G , Toga, Arthur W , Wright, Margaret J , Thompson, Paul M , Medland, Sarah E , Hsiung, Gink-Yuek , Jicha, Gregory A
Proceedings of the National Academy of Sciences | March 5, 2013 | Volume: 110 | Issue: 12 | Pages: 4768-4773
Aberrant connectivity is implicated in many neurological and psychiatric disorders, including Alzheimer’s disease and schizophrenia. However, other than a few disease-associated candidate genes, we know little about the degree to which genetics play a role in the brain networks; we know even less about specific genes that influence brain connections. Twin and family-based studies can generate estimates of overall genetic influences on a trait, but genome-wide association scans (GWASs) can screen the genome for specific variants influencing the brain or risk for disease. To identify the heritability of various brain connections, we scanned healthy young adult twins with high-field, high-angular resolution diffusion MRI. We adapted GWASs to screen the brain’s connectivity pattern, allowing us to discover genetic variants that affect the human brain’s wiring. The association of connectivity with the SPON1 variant at rs2618516 on chromosome 11 (11p15.2) reached connectome-wide, genome-wide significance after stringent statistical corrections were enforced, and it was replicated in an independent subsample. rs2618516 was shown to affect brain structure in an elderly population with varying degrees of dementia. Older people who carried the connectivity variant had significantly milder clinical dementia scores and lower risk of Alzheimer’s disease. As a posthoc analysis, we conducted GWASs on several organizational and topological network measures derived from the matrices to discover variants in and around genes associated with autism ( MACROD2 ), development ( NEDD4 ), and mental retardation ( UBE2A ) significantly associated with connectivity. Connectome-wide, genome-wide screening offers substantial promise to discover genes affecting brain connectivity and risk for brain diseases.